Association of MDM2 Overexpression in Ameloblastomas with MDM2 Amplification and BRAFV600E Expression.

Ameloblastoma is a rare tumor but represents the most common odontogenic neoplasm. It is localized in the jaws and, although it is a benign, slow-growing tumor, it has an aggressive local behavior and high recurrence rate. Therefore, alternative treatment options or complementary to surgery have been evaluated, with the most promising one among them being a targeted therapy with the v-Raf murine sarcoma viral oncogene homologue B (BRAF), as in ameloblastoma the activating mutation V600E in BRAF is common. Studies in other tumors have shown that the synchronous inhibition of BRAF and human murine double minute 2 homologue (MDM2 or HDM2) protein is more effective than BRAF monotherapy, particularly in the presence of wild type p53 (WTp53). To investigate the MDM2 protein expression and gene amplification in ameloblastoma, in association with BRAFV600E and p53 expression. Forty-four cases of ameloblastoma fixed in 10% buffered formalin and embedded in paraffin were examined for MDM2 overexpression and BRAFV600E and p53 expression by immunohistochemistry, and for MDM2 ploidy with fluorescence in situ hybridization. Sixteen of forty-four (36.36%) cases of ameloblastoma showed MDM2 overexpression. Seven of sixteen MDM2-positive ameloblastomas (43.75%) were BRAFV600E positive and fifteen of sixteen MDM2-positive ameloblastomas (93.75%) were p53 negative. All MDM2 overexpressing tumors did not show copy number alterations for MDM2. Overexpression of MDM2 in ameloblastomas is not associated with MDM2 amplification, but most probably with MAPK activation and WTp53 expression. Further verification of those findings could form the basis for the use of MDM2 expression as a marker of MAPK activation in ameloblastomas and the trial of dual BRAF/MDM2 inhibition in the management of MDM2-overexpressing/BRAFV600E-positive/WTp53 ameloblastomas.

Decoding a gene expression program that accompanies the phenotype of sporadic and basal cell nevus syndrome-associated odontogenic keratocyst.

BACKGROUND: Odontogenic keratocyst is characterized by local aggressive behavior and a high recurrence rate, as well as its potential to develop in association with the basal cell nevus syndrome. The aim of this study was to decode the gene expression program accompanying odontogenic keratocyst phenotype. METHODS: 150-bp paired-end RNA-sequencing was applied on six sporadic and six basal cell nevus syndrome-associated whole-tissue odontogenic keratocyst samples in comparison to six dental follicles, coupled with bioinformatics and complemented by immunohistochemistry. RESULTS: 2654 and 2427 differentially expressed genes were captured to characterize the transcriptome of sporadic and basal cell nevus syndrome-associated odontogenic keratocysts, respectively. Gene ontologies related to "epidermis/skin development" and "keratinocyte/epidermal cell differentiation" were enriched among the upregulated genes (KRT10, NCCRP1, TP63, GRHL3, SOX21), while "extracellular matrix organization" (ITGA5, LOXL2) and "odontogenesis" (MSX1, LHX8) gene ontologies were overrepresented among the downregulated genes in odontogenic keratocyst. Interestingly, upregulation of various embryonic stem cells markers (EPHA1, SCNN1A) and genes committed in cellular reprogramming (SOX2, KLF4, OVOL1, IRF6, TACSTD2, CDH1) was found in odontogenic keratocyst. These findings were highly shared between sporadic and basal cell nevus syndrome-associated odontogenic keratocysts. Immunohistochemistry verified SOX2, KLF4, OVOL1, IRF6, TACSTD2/TROP2, CDH1/E-cadherin, and p63 expression predominantly in the odontogenic keratocyst suprabasal epithelial layers. CONCLUSION: The odontogenic keratocyst transcriptomic profile is characterized by a prominent epidermal and dental epithelial fate, a repressed dental mesenchyme fate combined with deregulated extracellular matrix organization, and enhanced stemness gene signatures. Thus, we propose a developed epidermis-like phenotype in the odontogenic keratocyst suprabasal epithelial cells, established in parallel to a significant upregulation of marker genes related to embryonic stem cells and cellular reprogramming.

Influence of thyroxine supplementation on orthodontically induced tooth movement and/or inflammatory root resorption: A systematic review.

The role of thyroxine administration on orthodontically induced tooth movement and/or inflammatory root resorption remains unclear. The aim was to assess the influence of thyroxine administration on orthodontically induced tooth movement and/or inflammatory root resorption. The study protocol was registered in PROSPERO (CRD42020164151). An electronic search of indexed databases was conducted without time or language restrictions up to and including May 2020. The following eligibility criteria were imposed: (a) original prospective controlled clinical studies and/or experimental studies on animal models; (b) subjects undergoing orthodontic therapy with fixed appliances; (c) presence of a control group [orthodontic tooth movement without thyroxine administration]; and (d) intervention: orthodontic tooth movement with thyroxine administration. Review articles, commentaries, letters to the editor, case reports/series, studies with no control group, cross-sectional studies, retrospective studies and studies where thyroxine was administered along with other interventions such as calcitonin and prostaglandins were excluded. Quality of available evidence and risk of bias within studies were assessed. Any disagreements were resolved via consensus discussions. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 8 animal studies were included. Four studies reported that thyroxine administration increases the rate of orthodontic tooth movement; 3 studies did not show a significant difference. Three studies showed that thyroxine administration decreases orthodontically induced inflammatory root resorption; 2 studies found no significant difference. The risk of bias among studies was high. In conclusion, the influence of thyroxine administration on orthodontic tooth movement and/or orthodontically induced inflammatory root resorption in animal models remains unclear.

The immunohistochemical profile of basal cell nevus syndrome-associated and sporadic odontogenic keratocysts: a systematic review and meta-analysis.

OBJECTIVES: To provide a systematic review of the literature on studies comparing the immunoprofile of nevoid basal cell carcinoma syndrome (BCNS)-associated and sporadic odontogenic keratocysts (OKCs), in order to identify markers that could accurately distinguish the two OKC subtypes. MATERIALS AND METHODS: We searched MEDLINE/Pubmed, Web of Science, EMBASE via OVID, and grey literature for publications until December 28th, 2019, that compared the immunohistochemical expression of the two OKC subtypes. The studies were qualitatively assessed using the Critical Appraisal Tool for Case Series (Joana Briggs Institute). Sensitivity and specificity, positive and negative likelihood ratio, diagnostic odds ratio and area under the curve, and pooled estimates were calculated, using a random-effects model. RESULTS: Seventy-one studies were qualitatively analyzed; 61 markers were evaluated in one study and 32 in ≥ 2 studies. Twenty-five studies reported differential expression of 29 markers in the form of higher number of positive cells or greater staining intensity usually in BCNS-associated OKCs. Meta-analysis for bcl-2, Cyclin D1, CD56, CK18, p53, and PCNA showed that none of those markers is distinguishable between BCNS-associated and sporadic OKCs, in a 95% confidence interval. The risk of bias was high in 34 studies, moderate in 22, and low in 15. CONCLUSIONS: The present systematic review and meta-analysis uncovered that, although several immunohistochemical markers might characterize the OKC phenotype, they cannot discriminate between the BCNS-associated and sporadic OKCs. CLINICAL RELEVANCE: This study highlighted the requirement for additional screening for markers by immunohistochemistry, preferentially coupled to alternative diagnostic applications such as genomics technologies.

The relationship between Facebook behaviour and e-professionalism: A questionnaire-based cross-sectional study among Greek dental students.

INTRODUCTION: The social media attitude of health science students might affect patients' opinion about the health profession and have negative impact on e-professionalism. The aim of this study is to investigate the behaviour of Greek dental students on Facebook, focusing on potentially unprofessional posts and the online student-patient relationship. MATERIALS AND METHODS: Five hundred and twelve dental students in Greece answered an anonymous, 23-item questionnaire including multiple-choice questions about various topics, including Facebook profile settings and content shared by dental students, student-patient relationship via Facebook; and students' perception about the impact of their online behaviour. RESULTS: 93.2% of responders had a Facebook profile and 80.5% admitted that their online attitude might affect patients' opinion about dental profession. However, 71.7% posted pictures from holidays, 41.5% from nightclubs, and 26.2% photographs wearing swimwear/underwear, while 12.8% expressed online political party predilection. One quarter of students in clinical years were Facebook friends with patients and 58% and 30% of them had online discussion about topics related or not to dentistry, respectively, while 6.8% of dental students had posted defamatory comments about the dental school, faculty members or academic staff on Facebook. DISCUSSION: In accordance with studies in other countries, most Greek dental students had a Facebook profile and, although the majority realised the impact of Facebook behaviour on e-professionalism, a considerable percentage posted unprofessional content. CONCLUSION: Dental students might fall into pitfalls when it comes to e-professionalism. As social media are becoming an integral part of life, there is need to include e-professionalism in dental education curriculum.

Imaging of nano-hydroxyapatite/chitosan scaffolds using a cone beam computed tomography device on rat calvarial defects with histological verification.

OBJECTIVES: Τhis study aims at determining the ability of cone beam computed tomography (CBCT) to visualize critical-size defects (CSD) created at rat calvaria and filled with 75/25 w/w nano-hydroxyapatite/chitosan (nHAp/CS) scaffolds, prior to their histological investigation. MATERIALS AND METHODS: Thirty adult Sprague Dawley rats, 15 males and 15 females, were used. Two CSD, 5 mm in diameter, were bilaterally trephined in the parietal bone. The right CSD was filled with nHAp/CS scaffold, while the left CSD remained empty, as the control group. Two female rats died post-operatively. Rats were euthanized at 2, 4, and 8 weeks post-surgery. Twenty-eight specimens (15 × 2 × 10 mm) were resected-containing both CSDs-and then scanned using a NewTom VGi CBCT imaging unit (Verona, Italy). The manufacturer's software trace region profile tool (NNT v6.2, Verona, Italy) was used in selected axial slices. The greyscale value (in VGiHU) and the traced/selected region of interest (ROI, in mm2) of those areas were automatically calculated. Subsequently, all specimens were histologically examined. RESULTS: An increased VGiHU (P = 0.000), was observed in the experimental group relative to the control group. The ROI of CSD (in mm2) was significantly reduced (P = 0.001) from the fourth to the eighth week in both groups. No statistically significant difference between male and female rats (P = 0.188) was observed with respect to VGiHU. CONCLUSIONS: The nHAp/CS scaffolds are easily visualized using a particular high-resolution CBCT device. CLINICAL RELEVANCE: Both the CBCT measurements and also the histological results suggest that the nHAp/CS scaffold presence contributes to new bone formation in rat calvarial CSD.

Oral ulceration with bone sequestration: Retrospective study of eight cases and literature review.

OBJECTIVE: Oral ulceration with bone sequestration (OUBS) describes a site-specific intraoral ulcer that covers exposed, non-vital bone in patients lacking any etiological factor known to induce osteonecrosis. We aimed to conduct a retrospective study of eight new cases of OUBS and review the literature. SUBJECTS AND METHODS: This is a retrospective study of OUBS cases, diagnosed and managed during 2007-2017. Inclusion criteria were the presence of oral ulcer with exposed non-vital bone at sites of bone prominence and the absence of any factor known to cause osteonecrosis. The English literature was reviewed on original OUBS cases. RESULTS: Eight patients (5 males and 3 females, aged 27-75 years) were diagnosed with OUBS during years 2007-2017. Four cases involved the mandibular mylohyoid ridge, one a mandibular anterior exostosis and three the maxillary buccal/palatal exostoses. Exposed bone was removed under local anesthesia, resulting in complete healing in all cases. The literature review yielded 32 OUBS cases in the mandible. CONCLUSION: Oral ulceration with bone sequestration is a distinct, probably under-reported rather than rare clinical entity that should be regarded the provisional diagnosis in case of an oral ulcer covering exposed, non-vital bone at sites of bone prominence in patients lacking any etiological factor known to induce osteonecrosis.

Ductal cells of minor salivary glands in Sjögren's syndrome express LINE-1 ORF2p and APOBEC3B.

BACKGROUND: Type I interferon activation is a hallmark event in Sjögren's syndrome. L1 retroelements stimulate plasmacytoid dendritic cells, activating the type I interferons, and are regulated by various mechanisms, including the APOBEC3 deaminases. As L1s are potential trigger factors in autoimmunity, we aimed to investigate the immunohistochemical localization of L1 ORF2p and its inhibitor APOBEC3B protein in minor salivary glands of Sjögren's syndrome patients. METHODS: Twenty minor salivary gland-tissue samples from 20 Sjögren's syndrome patients, classified according to Tarpley's histological criteria, and 10 controls were evaluated for L1 ORF2p and APOBEC3B expression via immunohistochemistry. RESULTS: L1 ORF2p was expressed in 17/20 SS patients and all controls. APOBEC3B expression was observed in 15/20 Sjögren's syndrome patients, 5/5 chronic sialadenitis, and 3/5 normal minor salivary glands. Both antibodies stained the cytoplasm of the ductal epithelial cells. Negative staining was observed in the acinar cells. L1 ORF2p-positive immunostaining was significantly lower in Tarpley IV Sjögren's syndrome patients than controls (P = .039), and APOBEC3B-positive staining was significantly lower in Tarpley I compared to Tarpley II Sjögren's syndrome patients (P = .008) and controls (P = .035). CONCLUSIONS: L1 ORF2p and APOBEC3B are expressed in the ductal epithelial cells of minor salivary glands that are among the key targets in Sjögren's syndrome. L1 ORF2p expression may promote the L1 ability to act as an intrinsic antigen in Sjögren's syndrome. The potential future use of L1 ORF2-reverse transcriptase inhibitors in autoimmunity supports further investigation of L1 epigenetic regulation by APOBEC3 enzymes.

Localized Juvenile Spongiotic Gingival Hyperplasia: Report of Two Cases.

OBJECTIVE: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a painless gingival swelling that histologically exhibits hyperplasia of the non-keratinized stratified squamous epithelium, intercellular edema and spongiosis of the spinus layer, and exocytosis of inflammatory cells. LJSGH pathogenesis remains to be elucidated, while a possible origin from the gingival sulcus epithelium is nowadays proposed. STUDY DESIGN: We report two cases of LJSGH with immunohistochemical evaluation of cytokeratins (CKs) 18 and 19. RESULTS: Both cases concerned 12-year-old boys, who presented with a well-circumscribed bright red pedunculated papillary swelling on the marginal gingiva of the left maxillary lateral incisor. With the provisional diagnosis of LJSGH, the lesions were excised under local anesthesia and histological examination supported the final diagnosis of LJSGH. In both cases, the lesional epithelium showed intense and mild positivity for CK19 and CK18, respectively, while the adjacent normal gingival epithelium expressed CK19, but not CK18, only in the basal cell layer. The postoperative course was uneventful in both patients and no recurrence has been reported. CONCLUSION: LJSGH is a recently introduced entity that is worth attention in the clinical pediatric dentistry. Clinical and histological examination is required for the final diagnosis, while immunohistochemistry has shed light to LJSGH pathogenesis.

Anti-epidermal growth factor receptor targeted therapy-associated ulcerations.

The well-studied role of epidermal growth factor receptor (EGFR) in metastatic colorectal cancer (mCRC) and non-small cell lung cancer (NSCLC) has enabled the development of drugs that target this molecule, including panitumumab for the former and osimertinib for the latter. Oral adverse events due to those agents are rarely described in the literature and their exact characterization is hampered by inadequate reporting and/or incorrect terminology used. We report two cases of panitumumab- and osimertinib-associated oral ulcerations with emphasis on their possible pathogenesis and optimal management.

A graphite foreign body granuloma that caused palatal perforation. Case report and literature review.

Background: We present an unusual case of a graphite foreign body granuloma causing palatal perforation. Case description: A 62-year-old female presented with a macule on the hard palate clinically consistent with a blue nevus. On biopsy a black nodular mass was excised, establishing oroantral communication that was verified by a computed tomography scan. A diagnosis of malignant melanoma was strongly suspected, but microscopic examination showed a graphite foreign body granuloma. It was suggested that the graphite was implanted in a thin area of the palatal bone causing perforation. Conclusions: Graphite tattoos should be excised, both for diagnostics purposes and the possibility of causing tissue destruction by generating a foreign body granuloma reaction. Key words:Pencil core granuloma, graphite, foreign body, palate, case report.

Spongiotic Gingival Hyperplasia in a Child with Asperger Syndrome: a Case Report.

Background: Asperger syndrome is a type of autism spectrum disorder that may affect oral health and dental management. Spongiotic gingival hyperplasia is a rare lesion with unique clinicopathological features and unknown pathogenesis that has not been previously reported in a patient with autism spectrum disorder. The purpose of this case report is to present the first case of spongiotic gingival hyperplasia in a child with Asperger syndrome. Methods: A 14-year-old boy with Asperger syndrome was referred for diagnosis and management of bright red granular overgrowths of the marginal gingiva and interdental papilla of the mandibular right incisors and marginal gingiva of the mandibular left incisor. A biopsy was performed on the interdental papilla between the mandibular right incisors. Results: Microscopic examination and cytokeratin 19 immunopositivity confirmed the diagnosis of spongiotic gingival hyperplasia. The parents of the patient declined any further intervention, and four months later the gingival lesions, including the biopsied area, did not show any significant difference from the initial examination. Conclusions: Patients with autism spectrum diseases, such as Asperger syndrome, cannot achieve a good level of oral hygiene. Thus, it is expected that the incidence of spongiotic gingival hyperplasia should be higher in this group of patients, in case oral microbiome participates in its pathogenesis. Management of such lesions is challenging, as such patients do not comply with a proper oral hygiene program and do not cooperate with surgical excision.

The Stem Cell Expression Profile of Odontogenic Tumors and Cysts: A Systematic Review and Meta-Analysis.

BACKGROUND: Stem cells have been associated with self-renewing and plasticity and have been investigated in various odontogenic lesions in association with their pathogenesis and biological behavior. We aim to provide a systematic review of stem cell markers' expression in odontogenic tumors and cysts. METHODS: The literature was searched through the MEDLINE/PubMed, EMBASE via OVID, Web of Science, and CINHAL via EBSCO databases for original studies evaluating stem cell markers' expression in different odontogenic tumors/cysts, or an odontogenic disease group and a control group. The studies' risk of bias (RoB) was assessed via a Joanna Briggs Institute Critical Appraisal Tool. Meta-analysis was conducted for markers evaluated in the same pair of odontogenic tumors/cysts in at least two studies. RESULTS: 29 studies reported the expression of stem cell markers, e.g., SOX2, OCT4, NANOG, CD44, ALDH1, BMI1, and CD105, in various odontogenic lesions, through immunohistochemistry/immunofluorescence, polymerase chain reaction, flow cytometry, microarrays, and RNA-sequencing. Low, moderate, and high RoBs were observed in seven, nine, and thirteen studies, respectively. Meta-analysis revealed a remarkable discriminative ability of SOX2 for ameloblastic carcinomas or odontogenic keratocysts over ameloblastomas. CONCLUSION: Stem cells might be linked to the pathogenesis and clinical behavior of odontogenic pathologies and represent a potential target for future individualized therapies.

The Role of Macrophages in Oral Squamous Cell Carcinoma.

Oral cancer is a common malignancy worldwide, with high disease-related death rates. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral tumors, with surgical management remaining the treatment of choice. However, advanced and metastatic OSCC is still incurable. Thus, emphasis has been given lately in understanding the complex role of the oral tumor microenvironment (TME) in OSCC progression, in order to identify novel prognostic biomarkers and therapeutic targets. Tumor associated macrophages (TAMs) constitute a major population of the OSCC TME, with bipolar role in disease progression depending on their activation status (M1 vs. M2). Here, we provide an up to date review of the current literature on the role of macrophages during oral oncogenesis, as well as their prognostic significance in OSCC survival and response to standard treatment regimens. Finally, we discuss novel concepts regarding the potential use of macrophages as targets for OSCC immunotherapeutics and suggest future directions in the field.

The effect of nano-hydroxyapatite/chitosan scaffolds on rat calvarial defects for bone regeneration.

BACKGROUND: This study aims at determining the biological effect of 75/25 w/w nano-hydroxyapatite/chitosan (nHAp/CS) scaffolds on bone regeneration, in terms of fraction of bone regeneration (FBR), total number of osteocytes (Ost), and osteocyte cell density (CD), as well as its biodegradability. METHODS: Two critical-size defects (CSDs) were bilaterally trephined in the parietal bone of 36 adult Sprague-Dawley rats (18 males and 18 females); the left remained empty (group A), while the right CSD was filled with nHAp/CS scaffold (group B). Two female rats died postoperatively. Twelve, 11, and 11 rats were euthanized at 2, 4, and 8 weeks post-surgery, respectively. Subsequently, 34 specimens were resected containing both CSDs. Histological and histomorphometric analyses were performed to determine the FBR, calculated as [the sum of areas of newly formed bone in lateral and central regions of interest (ROIs)]/area of the original defect, as well as the Ost and the CD (Ost/mm2) in each ROI of both groups (A and B). Moreover, biodegradability of the nHAp/CS scaffolds was estimated via the surface area of the biomaterial (BmA) in the 2nd, 4th, and 8th week post-surgery. RESULTS: The FBR of group B increased significantly from 2nd to 8th week compared to group A (P = 0.009). Both the mean CD and the mean Ost values of group B increased compared to group A (P = 0.004 and P < 0.05 respectively). Moreover, the mean value of BmA decreased from 2nd to 8th week (P = 0.001). CONCLUSIONS: Based on histological and histomorphometric results, we support that 75/25 w/w nHAp/CS scaffolds provide an effective space for new bone formation.

Synchronous occurrence of two lateral periodontal cysts in the same patient. Report of a rare case and review of the literature.

We present a case of a patient with two lateral periodontal cysts in the maxilla and the mandible, respectively, and review the English literature on multiple lateral periodontal (LPCs) cysts and/or gingival cysts (GCs) and botryoid odontogenic cysts (BOCs). The patient was a 59 year-old female with two fluctuant swellings covered by semi-lucent mucosa on the attached gingiva between the maxillary and mandibular right canine and first premolar teeth, respectively. Periapical radiographs revealed at the respective sites between the roots of the canine and first premolar teeth areas unilocular radiolucencies. Intra-operatively, the presence of bone cavities was confirmed at both sites. The microscopic features were consistent with LPC. The review of the English literature on multiple LPCs and/or GCs and BOCs found seven reports of multiple LPCs, four of multiple GCs, and two with an LPCs and a GC. It is concluded that multiple LPCs have been rarely reported in the literature, but should be included in the differential diagnosis of multifocal radiolucencies lateral to vital teeth. The possibility of multiple lesions in different locations should direct to a thorough clinical and radiographic examination in a patient diagnosed with an LPC or GC. Key words:Jaw cysts odontogenic cyst, lateral periodontal cyst, multifocal unilocular radiolucencies.

Hypersensitivity reaction of the gingiva to chlorhexidine: case report and literature review.

OBJECTIVE: The aim of this case report was to document a case of delayed-type hypersensitivity reaction of the gingiva to chlorhexidine and review the literature on oral mucosal hypersensitivity reactions associated to chlorhexidine-containing oral hygiene products. STUDY DESIGN: A 58-year-old man presented with a well-demarcated erythematous area on the right upper anterior gingiva. Incisional biopsy was performed. Postoperatively, chlorhexidine digluconate gel was prescribed twice a day, but the patient did not use it because he experienced intense burning immediately after the first application. The microscopic diagnosis was nonspecific mucositis. Hypersensitivity reaction was suspected. The patient reported use of 0.004% chlorhexidine digluconate-based toothpaste twice a day in the past few years. A delayed-type hypersensitivity reaction to the toothpaste was hypothesized, and its use was discontinued. Chlorhexidine, the common ingredient of both the toothpaste and the gel, was considered the allergen. The literature was reviewed on chlorhexidine-induced oral hypersensitivity reactions. RESULTS: Two weeks after cessation of toothpaste use, complete remission of the lesion was observed without additional intervention. Four years later, no recurrence has been reported. The literature review yielded 7 studies reporting 20 patients with intraoral manifestations of hypersensitivity reactions associated with chlorhexidine-containing oral hygiene products. CONCLUSIONS: Clinicians should be aware that oral hygiene products containing even low concentrations of chlorhexidine might induce hypersensitivity reactions.

Fixed drug eruption on the tongue associated with piroxicam: report of two cases and literature review.

OBJECTIVE: The aim of this study was to describe 2 patients with piroxicam-associated fixed drug eruption on the tongue and to review the literature. STUDY DESIGN: Two females presented with recurrent ulcers after taking piroxicam for dysmenorrhea and pelvic pain. The English language literature was reviewed for cases of piroxicam-induced fixed drug eruptions, with a report on the site of occurrence. RESULTS: The ulcers reappeared in the identical lingual site after piroxicam intake; 3 times in patient #1 and 2 times in patient #2. Extraoral lesions were not observed. Following discontinuation of piroxicam, no relapse was reported. The literature review found 25 patients with piroxicam-associated fixed drug eruption. The oral mucosa/lips were affected in 8 patients who also had cutaneous/genital lesions. Solitary tongue involvement was not reported in any of them. Cross-sensitivity among different drugs of the same class is not unusual. CONCLUSIONS: Fixed drug reactions to piroxicam are rare, although nonsteroidal antiinflammatory drugs are among the most common causes of fixed drug eruptions. Of these rare fixed drug reactions to piroxicam, cutaneous lesions are reported much more often compared with oral mucosal lesions. Discontinuation of the causative drug is essential to promote healing and to avoid recurrences. Patients with history of piroxicam-induced fixed drug eruption should also avoid other oxicams because of potential cross-sensitivity.

Drug-associated hyperpigmentation of the oral mucosa: report of four cases.

OBJECTIVE: The aim of this study was to describe 4 patients with oral mucosa hyperpigmentation associated with 4 drug classes and to review the relevant literature. STUDY DESIGN: Two patients under imatinib and hydroxychloroquine treatment exhibited diffuse palatal hyperpigmentation and 2 patients treated with minocycline and golimumab showed multifocal pigmented macules. In all cases, biopsy was performed. RESULTS: Microscopically, in all cases, there was no increase in the number of melanocytes in the epithelium, and pigment granules were present in the lamina propria. The pigment granules in minocycline- and golimumab-associated hyperpigmentation were seen in the superficial lamina propria and reacted for silver but not iron, whereas in imatinib- and hydroxychloroquine-associated hyperpigmentation, pigment granules were found in the reticular lamina propria and reacted for both silver and iron. A review of the literature found 38 cases of hyperpigmentation of the oral mucosa attributed to minocycline, 23 to imatinib, 1 to hydroxychloroquine without microscopic documentation, and none to golimumab. CONCLUSIONS: The temporal relationship between pigmentation and onset of drug effect, resolution following drug withdrawal, and exclusion of other causes support the diagnosis of drug-induced hyperpigmentation. Microscopic examination may be contributory to diagnosis, as there are differences among drugs with regard to the distribution of pigment granules and the histochemical reactions of the drugs.

Spongiotic Gingival Hyperplasia Synchronously Involving Multiple Sites: Case Report and Review of the Literature.

Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a gingival lesion with unique clinicopathologic features that may involve synchronously multiple sites. We present a case with lesions clinically consistent with LJSGH in four jaw quadrants, confirmed by biopsy and review the English literature on multifocal LJSGH cases. A 19 year-old woman presented with circumscribed, erythematous overgrowths on the right and left maxillary and mandibular gingiva. With the provisional diagnosis of multifocal LJSGH, total excision of four maxillary lesions was performed. Clinical, microscopic and immunohistochemical examination with cytokeratin 19 confirmed the diagnosis of LJSGH in multiple sites. The excised lesions showed partial to complete recurrence after 4 months, while spontaneous regression of all but one lesion was observed after 15 months. Twenty cases with synchronous involvement of the gingiva of at least two teeth were previously reported. Their clinical features were comparable to that of solitary LJSGH. Only one case involved all four jaw quadrants. Spontaneous remission has not been documented before. The recognition of multiple lesions with clinicopathologic features diagnostic of LJSGH in the same adult patient argue against the designations "localized" and "juvenile". Recurrences are common, while remission might occur.