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.

Richter transformation in the oral and maxillofacial area: report of 2 cases and literature review.

Richter transformation (RT) is a term used to refer to the development of an aggressive lymphoma, usually of diffuse large B-cell lymphoma type, in a patient with a history of chronic lymphocytic leukemia. It may present with heterogeneous manifestations, including the occurrence of tumors at extranodal sites. To date, only 6 cases of RT involving the oral and maxillofacial region have been reported. Here, we present 2 rare cases of lymphoma initially affecting the maxilla and the lower gingiva, respectively, of female patients with chronic lymphocytic leukemia and review the English language literature about RT manifesting in the oral and maxillofacial tissues.

Assessment of TLR4 and TLR9 signaling and correlation with human papillomavirus status and histopathologic parameters in oral tongue squamous cell carcinoma.

OBJECTIVES: Toll-like receptors (TLRs) may promote or inhibit tumor progression. The aim of this study was to assess the expression of TLR4 and TLR9 and their downstream targets in oral tongue squamous cell carcinoma (OTSCC) in correlation with histopathologic parameters and human papillomavirus (HPV) status. STUDY DESIGN: OTSCC (fully or superficially invasive and in situ) were studied. Immunohistochemical expression of TLR4, TLR9, nuclear factor-κΒ (NF-κΒ/p65), and interferon-ß (IFN-ß) was evaluated in tumor and inflammatory cells and in adjacent morphologically normal mucosa. HPV status was also determined. RESULTS: TLR4 showed increased expression levels in tumor and infiltrating inflammatory cells compared with adjacent mucosa, especially in fully invasive cases; a negative correlation between TLR4 levels in inflammatory cells and tumor grade was observed. TLR9 was upregulated in tumor and infiltrating inflammatory cells compared with the adjacent mucosa; its expression in inflammatory cells was higher in well differentiated tumors. NF-κΒ and IFN-ß were elevated in cancerous tissues, especially in fully invasive cases, and positively correlated with TLR4 and/or TLR9. HPV positivity (detected in 15.9% of the cases) demonstrated positive correlation with TLR9 and NF-κΒ levels. CONCLUSIONS: TLR4 and TLR9 are upregulated in OTSCC and its microenvironment and, by affecting important downstream molecules, such as NF-κB and IFN-ß, may play a role in oral cancer development and progression.

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.

Oral Verruciform Xanthoma within Lichen Planus: A Case Report and Literature Review.

BACKGROUND: Verruciform xanthoma is an uncommon benign tumor, which exhibits a wide range of clinical patterns. The occurrence of the lesion in patients with immune-mediated mucocutaneous diseases may suggest a role of localized epithelial cell damage and chronic inflammation in its pathogenesis. CASE REPORT: A case of verruciform xanthoma on the tongue of a 56-year-old female with oral lichen planus is reported. An asymptomatic pink-white lesion with a granular surface was observed in the left lateral lingual border, which was closely associated with a white plaque and striae. An incisional biopsy was performed, and histologically, epithelial projections in a verrucous pattern were observed. In the subepithelial connective tissue, aggregates of foamy cells that exhibited immunoreactivity for CD68 were noted. The final diagnosis was verruciform xanthoma. The mucosa adjacent to the lesion demonstrated histopathological features consistent with lichen planus. CONCLUSIONS: A total of twelve cases of oral verruciform xanthomas in patients with oral lichen planus including the present case have been reported in the literature. The clinician should be aware that verruciform xanthoma may mimic malignancy, and therefore, biopsy is required for definitive diagnosis to be established, especially when this tumor develops within conditions that show potential for malignant transformation.

Alterations in the expression of DNA damage response-related molecules in potentially preneoplastic oral epithelial lesions.

OBJECTIVES: The aim of this study was to evaluate the expression levels of DNA damage response (DDR) markers in potentially preneoplastic oral epithelial lesions (PPOELs). STUDY DESIGN: Immunohistochemical expression of DDR markers (γΗ2 ΑΧ, pChk2, 53 BP1, p53, and phosphorylated at Ser 15 p53) was assessed in 41 oral leukoplakias, ranging from hyperplasia (H) to dysplasia (D) and in comparison with oral squamous cell carcinoma (OSCC) and normal mucosa (NM). Statistical and receiver operating characteristic curve analysis were performed. RESULTS: γH2 AX immunoexpression demonstrated a gradual increase and upper layer extension from NM to H to higher D degrees to OSCC. pChk2 expression was minimal in NM, relatively low in PPOELs, with an increasing tendency from H to D, and higher in OSCC. 53 BP1 demonstrated higher levels in OSCC than in NM, whereas its expression in PPOELs was heterogeneous, gradually increasing according to D. p53 demonstrated progressively higher levels and upper layer extension from H to D to OSCC. Phosphorylated p53 was absent in NM and relatively low in PPOELs and OSCC. CONCLUSIONS: DDR markers' expression is variable in PPOELs, showing a tendency to increase along with dysplasia. Activated DDR mechanisms may play an important protective role at early stages of oral carcinogenesis, but probably suffer progressive deregulation, eventually failing to suppress malignant transformation.

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.

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.

Multiple primary squamous cell carcinomas of the lower lip and tongue arising in discoid lupus erythematosus: a case report.

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

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.

A preliminary immunohistochemical study of signal transducer and activator of transcription (STAT) proteins in primary oral malignant melanoma.

OBJECTIVE: Primary oral malignant melanoma (POMM) is a rare type of malignancy with a very poor prognosis, the molecular pathogenesis of which remains elusive. The aim of this study was to assess the expression status of signal transducer and activator of transcription (STAT) proteins in POMM. STUDY DESIGN: Six POMMs were included in the study. Total protein levels of STAT1, STAT3, and STAT5a, as well as the tyrosine phosphorylated (activated) form of STAT3 (pSTAT3), were assessed immunohistochemically. RESULTS: Immunohistochemical evaluation of total STAT3 revealed diffuse and strong cytoplasmic and nuclear expression in the majority of tumor cells of all cases, whereas activated pSTAT3 had mostly mild nuclear expression in 5%-40% of malignant melanocytes in all cases. Evaluation of STAT1 and STAT5a identified mainly mild cytoplasmic expression in the absence of nuclear localization. CONCLUSION: The identification of aberrant STAT3 expression and activation in oral malignant melanocytes supports a possible role of this molecule in POMM. In contrast, STAT5a has only limited cytoplasmic expression, mitigating against its involvement in POMM. Also, STAT1's low levels may have implications for POMM sensitivity to interferon-based therapeutic strategies, considering the role of this molecule in cutaneous melanoma immunotherapy.

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.

MALT Lymphoma of Minor Salivary Glands in a Sjögren's Syndrome Patient: a Case Report and Review of Literature.

BACKGROUND: Sjögren's syndrome is a chronic systemic disease, characterized by lymphocytic infiltration and destruction mainly of the salivary and lacrimal glands, resulting in xerostomia and xeropthalmia. Sjögren's syndrome patients have a 44-fold excess risk for the development of non-Hodgkin's lymphoma particularly mucosa-associated lymphoid tissue (MALT) lymphoma, prevalently affecting the major salivary glands. In this report, a rare case of MALT lymphoma of minor salivary glands in a patient with Sjögren's syndrome is described. A review of the published cases of MALT lymphoma located in the minor salivary glands of patients with Sjögren's syndrome is provided. METHODS: In a 64-year-old female patient previously diagnosed with Sjögren's syndrome, an asymptomatic soft tissue mass at the palate was noticed, exhibiting rapid enlargement within one month. With a main differential diagnosis of salivary gland neoplasm or lymphoproliferative lesion, a partial biopsy was performed accompanied by proper immunohistochemical analysis. RESULTS: A final diagnosis of MALT lymphoma was rendered and the patient was referred for further multidisciplinary evaluation. Gastric endoscopy and biopsy revealed a Helicobacter pylori-negative gastric MALT lymphoma, while spleen involvement and bone marrow infiltration were also identified. Patient was classified as having stage IV disseminated disease and a standard chemotherapy protocol was administered; the treatment was well tolerated and resulted in complete remission. CONCLUSIONS: This case emphasizes the need for close monitoring of patients with Sjögren's syndrome by oral medicine specialists, which, besides ensuring proper management of xerostomia and its sequelae, may also lead to early recognition of lymphoma development.

Ossifying Fibromyxoid Tumor of the Retromolar Trigone: A Case Report and Systematic Review of the Literature.

Ossifying fibromyxoid tumor (OFMT) is a mesenchymal neoplasm of uncertain lineage and intermediate biologic behavior. Involvement of the head and neck area is infrequent (10% to 15%) and intraoral presentation is very rare. An OFMT developing in the retromolar trigone of a 13-year-old male is presented, along with a comprehensive review of oral OFMT cases. Among 12 oral OFMTs (including the present case), most patients were male (72.7%), with a mean age of 30.3 (13-67) years. The tumors generally appeared as painless masses of firm or hard consistency (mean diameter 27.7 mm), most commonly located in the soft tissues of the mandible (50%). Common microscopic features included ossification, lack of atypia or high mitotic activity, and immunohistochemical positivity for S100 (5/7), vimentin (6/6), GFAP (3/6), and SMA (2/6). Recurrence was reported only in one case. Further characterization of this rare entity is needed to increase our understanding of its distinct clinical and histopathologic features.

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.

Transient lingual papillitis: A retrospective study of 11 cases and review of the literature.

BACKGROUND: Transient lingual papillitis (TLP) is a common, under-diagnosed, inflammatory hyperplasia of one or multiple fungiform lingual that has an acute onset, and is painful and transient in nature. MATERIAL AND METHODS: Eleven cases of TLP were diagnosed based on their clinical features. Information on demographics, clinical characteristics, symptoms, individual or family history of similar lesions, medical history, management and follow-up were extracted from the patients' records. The English literature was reviewed on TLP differential diagnosis, pathogenesis and management. RESULTS: The study group included 8 females and 3 males (age: 10-53 years, mean age 31.7±12.88 years). Seven cases were classified as generalized form of TLP and 4 as localized form. Nine cases were symptomatic. Time to onset ranged from 1 to 14 days. A specific causative factor was not identified in any case and management was symptomatic. CONCLUSIONS: Although TLP is not considered as a rare entity, available information is limited. Diagnosis is rendered clinically, while biopsy is required in cases with a differential diagnostic dilemma. TLP should be included in the differential diagnosis of acute, painful tongue nodules. Key words:Transient lingual papillitis, fungiform papillary glossitis, tongue, nodules.

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.

Recurrence in a patient with a 10-year history of sinonasal mucosal melanoma manifesting as facial swelling.

Sinonasal mucosal melanoma is a rare tumor that develops slowly and may manifest with non specific signs and symptoms, causing significant delay in diagnosis. Local recurrence is common and usually occurs within the first two years after the initial treatment. Prognosis of recurrent lesions is poor and 5-year survival ranges between 10-47%. We report the clinical, radiographic, histopathological and immunohistochemical findings of a recurrent sinonasal mucosal melanoma which was diagnosed 10 years after the initial treatment, in a patient who presented with unilateral facial swelling and one-sided difficulty in breathing of two years duration. We discuss the causes of late diagnosis and review the negative predictive factors for recurrence and survival. As early diagnosis is of paramount importance for prognosis, we emphasize the signs and symptoms of patients with a history of sinonasal mucosal melanoma which should raise the suspicion for recurrence, in spite of a long time interval since diagnosis. Key words: Mucosal melanoma, nasal cavity, sinus, recurrence.

Evidence for APOBEC3B mRNA and protein expression in oral squamous cell carcinomas.

It has been demonstrated that APOBEC3B possesses cytidine deaminase activity, which is likely to result in C-to-T signature mutations. Increased expression of the APOBEC3B gene has been shown to correlate with higher incidence of such mutations in various cancer types, such as breast, bladder, lung, and head and neck carcinomas. In the current study, we used in silico methods, immunohistochemistry and qRT-PCR to detect the presence of APOBEC3B signature mutations and examine the levels and patterns of APOBEC3B expression in oral squamous cell carcinomas (OSCCs). Using the Cancer Genome Atlas (TCGA) database, we have found a high incidence of C-to-T transitions in head and neck squamous cell carcinomas (HNSCCs), of which OSCCs constitute the largest subgroup. Additionally, we compared APOBEC3B expression, at both mRNA and protein level, between OSCCs and non-cancerous samples. APOBEC3B was detected in both groups, but nuclear localization was consistent only in normal oral cells. APOBEC3B mRNA levels were clearly higher in OSCCs than in controls. These results suggest that while in normal oral cells APOBEC3B has an important nuclear function to fulfill, this activity may be hindered in a subgroup of tumor cells, due to the more prominent localization of the enzyme in the cytoplasm.

Langerhans cell histiocytosis mimicking aggressive periodontitis: Challenges in diagnosis and management.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of Langerhans cells that affects various organs. Oral involvement may simulate periodontal disease and cause significant diagnostic and management difficulties. Here, we present an interesting LCH case with severe periodontal destruction in a young woman in order to facilitate early recognition of this aggressive disease and successful participation of the general practitioner in the management of such patients. CASE PRESENTATION: A 21-year-old woman was referred for evaluation of recurrent episodes of dull pain in the gingiva for the last 9 months, which had not been successfully managed by her general practitioner. Clinical and radiographic examination showed extensive alveolar bone loss. Histopathologic examination revealed diffuse aggregates of Langerhans cells, while a complete work-up did not demonstrate evidence of systemic involvement. A diagnosis of LCH limited to the oral cavity was established. The patient received systemic chemotherapy in combination with appropriate dental care including gingival debridement and tooth immobilization. Following chemotherapy completion, comparative clinical, radiographic, and microscopic evaluation showed complete remission. During an 18-month follow-up period, frequent oral examinations and appropriate dental interventions confirmed the lack of LCH recurrence and guaranteed the stabilization of periodontal tissues. CONCLUSIONS: Oral soft and hard tissue involvement may be the only manifestation of LCH. The present case exemplifies the importance of close collaboration between general dentistry and its disciplines (periodontology, restorative dentistry, oral medicine, oral and maxillofacial pathology, and oral radiology), and hematology-oncology for diagnosis, management, treatment monitoring, and decision-making.