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The objectives were to characterize clinico-pathologically a large series of peri-implant peripheral giant cell granuloma (PGCG), and investigate the role of foreign material as a possible etiological factor.The study was retrospective, conducted on peri-implant specimens submitted for histology between 2005 and 2021.Three hundred and thirty-five peri-implant biopsies were retrieved, of which 52 (15.5%) were PGCG. The study population included 28 females and 24 males, age 35-92 years, mean 61. 51.2% reported bone involvement. The lesion involved the margins of the specimen in 65.3%, recurrence was reported in 46.1%. In 58.8% the implant was removed at the same time the specimen was submitted for histopathological analysis. Small foci of black granular foreign material were observed in 53.8% of cases of which 67.8% were birefringent under polarized light. The foreign material granules were not ingested inside multinucleated giant cells, but were scattered in the stromal compartment.Peri-implant PGCG is locally aggressive, with frequent bone involvement and high recurrence rate, resulting in implant loss in the majority of cases. The high recurrence rate may be related to conservative or inadequate surgery. Foreign material although common does not seem to have a role in its development.

Compare recognized microscopic parameters, including variations in width, plaque-like thickenings, intra-epithelial microcysts, clefts, mucous, hob-nail, ciliated and clear cells, between glandular odontogenic cyst (GOC) and GOC-like cysts, investigate the extent of cyst circumference exhibiting these features, and inflammation.Archival records of cysts with histological features of GOC evaluated between 2000 and2020 were retrieved. Slides were revised, and the expression of features throughout the cyst wall was analyzed. Cysts with at least 5 features were classified as GOC, cysts with 3-4 features as GOC-like.The study included 74 cysts, 47 males M, 25 females (2 unknown gender), aged 19-81 years, 62 (83.8%) GOC, 12 (16.2%) GOC-like. Mandible was involved in 44 (59.5%), maxilla in 30 (40.5%), 18 (25%) were associated with unerupted teeth. Cyst classified as GOC had significantly higher rates of all parameters investigated, (except ciliated and clear cells), than GOC-like cysts (p ≤ 0.05). 26 (40.6%) cases showed GOC features in50% of cyst circumference, 21 (32.8%) involved 25-50%, 17 (26.6%)25%. More than 50% circumference involvement was highly and independently predictive for a diagnosis of GOC,25% was highly and independently predictive for GOC-like (p = 0.003). Hobnail cells (p = 0.008) and plaque-like thickenings (p = 0.038) were significantly more frequent in inflamed cysts.Besides the number and type of histological features, GOC can be characterized by their distribution within the cyst circumference (focal Vs diffuse), and it may serve as a new diagnostic aid. It is suggested that GOC and GOC-like may represent a single spectrum.

We aimed to collect and analyze available cases of intraoral acantholytic squamous cell carcinoma (aSCC), that consisted of the authors’ cases and cases derived from the existing literature, with an emphasis on the pathological staging and patient outcome. Our research question was whether aSCC is more aggressive than conventional SCC. The literature was searched for documented cases of aSCC involving the intra-oral mucosa, excluding those from the lips and tonsils, and seven new cases were added from our files. The authors compared the obtained aSCC data to existing data for conventional SCC. Fisher Exact or Pearson’s χ(2) tests were used for categorical variables. Fifty-five cases of intraoral aSCC were reviewed, of which 48 were retrieved from the literature. Analysis of the published cases was reinforced by contacting the authors of all the papers with incomplete data for further clarifications. The most common sites of aSCC were the tongue (24/55) and the maxilla/maxillary gingiva and/or palate (11/55). The overall survival rate was 36/53 (67.9%) with a mean follow-up period of 22 months against 62.5% for conventional SCC (p = 0.6). No statistically significant difference between the two variants of the tumor with respect to the oral cavity was detected. The differences in age, sex, survival rate, staging, and locations were not statistically significant. Based on the available data from 55 cases, there is no evidence to suggest that aSCC is more aggressive than conventional SCC in intraoral cases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12105-021-01368-8.

Medication-related osteonecrosis of the jaws (MRONJ) is a well-known complication that, in the majority of cases, is related to antiresorptive agents. Numerous articles have described cases of MRONJ in bisphosphonate-naive patients treated with anti-angiogenic agents administered via various routes. A single case of MRONJ after intravitreal injection of bevacizumab has been reported. We report a case of MRONJ after intravitreal injection of a different anti-angiogenic agent - ranibizumab - for the treatment of neovascular age-related macular degeneration, in a bisphosphonate-naive patient. Although it may be a rare complication, patients treated with multiple doses of anti-angiogenic agents should be monitored for the possible early diagnosis of MRONJ.

Exophytic lesions of the tongue encompass a diverse spectrum of entities. These are most commonly reactive, arising in response to local trauma but can also be neoplastic of epithelial, mesenchymal or miscellaneous origin. In most cases, the microscopic examination is likely to provide a straightforward diagnosis. However, some cases can still raise microscopic diagnostic dilemmas, such as conditions that mimic malignancies, benign tumors with overlapping features and anecdotal lesions. A series of "lumps and bumps" of the tongue are presented together with suggested clues that can assist in reaching a correct diagnosis, emphasizing the importance of the clinico-pathological correlations.

OBJECTIVES/HYPOTHESIS The effects of different electrocautery power settings on mucosal contraction and margin status in the oral cavity have not been well established. The aim of this study was to examine how different levels of electrocautery energy outputs affect oral mucosal tissue margins. STUDY DESIGN Animal model. METHODS A model of 23 adult rats was used (two specimens per rat). After anesthetizing the animals, a 6-mm biopsy punch marked the resection margin on the buccal mucosa (one per cheek). The specimens were excised by means of three energy levels, a cold knife, and monopolar diathermy that was set on either 20 W or 30 W cut modes. The specimens were evaluated for extent of contraction. RESULTS A total of 45 samples were obtained and measured, including 15 specimens in the cold-knife group, 15 specimens in the 20 W group, and 15 specimens in the 30 W group. The median diameters of the specimens after resection were 4.5 mm for the cold-knife group (interquartile range [IQR] = 4.0-5.0), 3.5 mm for the 20 W group (IQR = 3.5-4.0), and 2.8 mm for the 30 W group (IQR = 2.5-3.0). Specimen contraction was 25.0%, 41.7%, and 53.3%, respectively. The difference in shrinkage between each pair was statistically significant: cold knife versus 20 W, P = .001; cold knife versus 30 W, P

Angiolipoma, distinguishable from other lipomas by its excessive degree of vascular vessels, are rare in the head and neck and require unique management. A slow growing mass, located underneath the inferior border of the right mandibular angle of a 51-year-old female, was excised under general anesthesia. Unexpected excessive bleeding during the excision was observed and the histological specimen was diagnosed as angiolipoma. As shown in this case report, pre-operative imaging modalities have a crucial influence and are sufficient to diagnose and manage angiolipomas. The “Gold standard” treatment is excision with clear margins and bleeding management should be taken into account according to appropriate differential diagnosis.

Plexiform ameloblastoma is a locally aggressive odontogenic tumor, rare in the anterior mandible. The treatment of choice is resection with 1–3 cm free margins. In most of reported cases, the affected mandible is reconstructed by autogenic bone graft or osseocutaneous microvascular free flap in order to return function and esthetics. Case description: A 2 cm diameter exophytic ameloblastoma, located in the anterior mandible of a 50-year-old male was resected and reconstructed in a unique manner—allogenic bone block, recombinant human bone morphogenetic protein (rhBMP) and xenograft particles via transcutaneous submental approach. After bone maturation, dental implants were placed and restored by fixed prosthetics. Practical implications: Mandible reconstruction modalities have a crucial influence on patient quality of life, function and esthetics. Allogenic bone block combined with rhBMP and xenograft particles can replace the traditional autogenous bone in certain circumstances. A submental transcutaneous “tent pole” approach can improve the success rate of the reconstruction procedure.

Fibrosis is a recognized complication of chronic inflammatory conditions, which has not yet been described in oral lichen planus. To describe characteristics of submucosal fibrotic bands in oral lichen planus. Prospective study. Patients with biopsy confirmed lichen planus were included. Clinical examination recorded fibrotic bands, mouth opening, vestibular depth loss, gingival recessions adjacent to band, lichen subtypes, areas of affected mucosa, extra-oral manifestations. Patients completed the Chronic Oral Mucosal Disease Questionnaire, with additional questions regarding stiffness, restricted opening, symptom frequency, time from diagnosis of lichen, co-existing medical conditions. 73 patients were included, 14 M, 59 F, age 28–84 (mean 61) years. Buccal fibrous bands were palpated in 22 (30.1%), 13 (59%) were bilateral. Self-reported restricted opening/stiffness were significantly associated with fibrous bands (36% Vs. 11% in controls, p = 0.02). Mouth opening less than 40 mm was recorded in only 2 (9%) with bands, none in controls. Reduced vestibular depth was significantly associated with bands (11 (50%) Vs 3 (6%) in controls, p = 0.0001).Gingival recessions adjacent to bands were recorded in 3 (13.6%). No association was demonstrated between fibrous bands and erosive lesions, extra oral involvement, smoking, age, visual analogue scale, quality of life questionaire and disease duration. Histological evaluation of one case each with and without band and control showed increased mean width of connective tissue. Submucous fibrous band is first described in the present study. It is common in oral lichen planus, may lead to feeling restricted mouth opening, stiffness, loss of vestibular depth and adjacent gingival recession.

Background and Objectives: Peri-implantitis is a common finding among patients with dental implants. There is no consensus regarding the treatment of this disease, but in many cases, surgical treatment is common practice. A histopathological analysis is not an integral part of suggested protocols. The present study investigated the clinical and histopathological parameters of lesions mimicking peri-implantitis and correlated them with the outcome and follow-up data. Materials and Methods: The study included 65 consecutive biopsies taken from peri-implantitis patients between 2008–2019. Results: The three common diagnoses were fibro-epithelial hyperplasia 20 (30.7%), pyogenic granuloma 16 (24.6%), and peripheral giant cell granuloma 15 (23%). There were 18 cases of recurrent lesions in the study group (27.7%). The recurrence rate was the highest in peripheral giant cell granuloma (8, 12.3%), versus 6% in pyogenic granuloma and fibro-epithelial hyperplasia. These differences in the recurrence rate were statistically significant (p = 0.014). Conclusions: This study emphasizes the necessity of submitting tissue of peri-implantitis cases for histopathological analysis since the more locally aggressive lesions (peripheral giant cell granuloma and pyogenic granuloma), which comprise nearly half of the cases in this study, do not differ in clinical or radiographic characteristics from other peri-implant lesions.

Introduction White/red lesions, exophytic masses with or without ulceration, are well-recognized typical presentations of oral squamous cell carcinoma (OSCC). Rarely, clinical characteristics may mimic benign lesions. Objective To report an unusual case of OSCC of the anterior maxillary gingiva and hard palate, with an initial nonspecific clinical and histologic presentation mimicking benign inflammatory lesions. Case Presentation A 58-year-old, otherwise healthy woman was referred with mild pain and a reddish, papillary, gingivopalatal, inflammatory-like lesion of 6 months’ duration. Medications, systemic medical conditions, tobacco use, and parafunctional habits that could generate the appearance were excluded. Radiographs did not reveal any bone involvement. Repeated periodontal treatment, improvement of oral hygiene, topical applications of disinfectant, an antifungal, and corticosteroids all failed to yield any improvement. During a period of 18 months, 3 biopsies were taken from the affected gingiva, showing only benign epithelial hyperplasia with dense chronic inflammation devoid of any evidence of malignancy. Following rapidly progressing tooth mobility of the lateral incisor concomitant with accelerated overgrowth of the anterior palatal gingiva, dental radiography was repeated, and computed tomography was performed. Both revealed an extensive osteolytic lesion in the premaxilla. A new biopsy taken from the affected gingiva and adjacent maxillary alveolar bone yielded a diagnosis of OSCC. Treatment included resection of the premaxilla and floor of the nose with bilateral neck dissection. Conclusions This case emphasizes the possibility of a deceptive initial appearance of OSCC, the sudden burst and rapid disease progression, and the importance of close follow-up of unusual nonspecific inflammatory-like processes in the oral cavity.

Background Xerostomia resulting from medications or systemic disorders may differ in histopathologic findings. Objective To compare clinical and pathological features from patients with xerostomia and minor salivary gland biopsies and search for features suggesting IgG-related disease. Materials and Methods Retrospective analysis of consecutive biopsies between 2009 and 2017. Histomorphometry included glandular architecture, fibrosis, fat replacement, inflammation density, plasma cells, and IgG/IgG4 in selected cases. Results The study included 64 cases, 18 male and 46 female patients, with a mean age of 56. Biopsy was taken for suspected Sjogren syndrome (SS) in 58 cases (91%). Fifty-four biopsies had adequate specimen for SS evaluation; only 12 met microscopic criteria supporting SS (22.2%). Polypharmacy (>3 drugs) was found to be inversely related to SS (P = .05). The majority of the entire study group had various systemic conditions (63%), most often hyperlipidemia and high blood pressure (28% each). The use of medications was recorded in 66%, 50% of which used 2 or more. Fat replacement, fibrosis, and acinar atrophy showed significant correlations with increased age (P Conclusions SS was confirmed in only 22% of cases. Increased age correlated with acinar atrophy, fat replacement, and fibrosis, explaining xerostomia in older patients without SS. Hyperlipidemia showed associated fat replacement. Polypharmacy was significantly more common in non-SS cases. Attention to the patient's medical history and medications used may lead to correct diagnosis, reducing the need for lip biopsy in the majority of cases.

Purpose Different lesions in the fibro-osseous group share microscopic features; thus, establishing a definitive diagnosis based on microscopic features alone can be a challenge. There is a need for additional microscopic tools to aid in differentiating these lesions. This study compared parameters related to vascularity among 3 lesions in the fibro-osseous group: fibrous dysplasia (FD), central ossifying fibroma (COF), and cemento-osseous dysplasia (COD). Materials and Methods This study was a cross-sectional analysis of biopsied lesions retrieved from 3 medical centers over a 14-year period. The primary predictor variables were the vascularity parameters (number, perimeter, and area). The outcome variables were diagnoses of FD, COF, and COD. Diagnosis was based on clinical, microscopic, and radiologic correlations. From each histopathologic slide, 5 representative fields were captured with a computerized digital camera. The number of blood vessels was counted, and the surface area and vascular perimeter were measured by tracing the perimeter of each vessel. Data were statistically analyzed using analysis of variance with logarithmic transformation and a Tukey adjustment. Results Sixty-six cases were included in the study (26 in FD group, 26 in COF group, and 14 in COD group). The mean number of vessels showed only a tendency to be larger in the FD group compared with the COF and COD groups (5.4 ± 2.6, 3.7 ± 2.3, and 3.6 ± 1.7, respectively), but the results did not reach the threshold for significance. The mean vascular perimeter was 1,385.8 ± 859.2 pixels in the FD group and 742.6 ± 661.8 in COF group after logarithmic transformation (P = .012). The perimeter in the COD group was smaller (941.1 ± 502) compared with that in the FD group, but the difference did not reach the threshold for significance. The mean area was 25,061 ± 24,875.6 in the FD group and 11,773.8 ± 21,734.4 in the COF group after logarithmic transformation (P = .004). The perimeter in the COD group was smaller (13,011.1 ± 8,338.3) compared with the FD group, but the difference did not reach the threshold for significance. Conclusion The vascular content of the FD group was markedly higher than of the COF group. These vascular changes can aid in differentiating these lesions microscopically.

Mucous membranous pemphigoid (MMP) is an autoimmune disease of the mucous membranes characterized by formation of subepithelial blisters. MMP commonly involves the ocular and oral mucosa. Laryngeal MMP is very rare, estimated as occurring in 1 of 10 million persons in the general population. It mostly affects the supraglottis, but may also involve other laryngeal sites as well as extralaryngeal areas. This report describes the clinical picture, workup to diagnosis, and differential diagnosis of an isolated epiglottic process in an elderly female who presented with isolated, long-standing, nonresolving epiglottitis, later diagnosed as MMP with epiglottal and oral involvement.

Long standing, asymptomatic, well-demarcated erythema of the hard palate with a histopathological psoriasiform pattern comprises a challenging diagnosis. We present a series of patients with such clinical and histological findings and discuss the possible diagnoses. We collected all patients with palatal erythematous lesions that had well-documented clinical examination. Excluded were patients with definitive diagnosis of oral infections (e.g. candidiasis), neoplastic/pre-neoplastic lesions, auto-immune diseases, reactive lesions, blood disorders and vascular malformations. Thirteen patients (six females, seven males, age range 11–56 years) were included. Histopathologically, a psoriasiform pattern was observed in all biopsied lesions. One patient was diagnosed with hereditary mucoepithelial dysplasia (HMD) and four with cutaneous psoriasis. The remaining eight patients were otherwise healthy. A combination of persistent, asymptomatic palatal erythematous lesion with psoriasis-like histopathology may represent an oral manifestation of HMD or psoriasis, concomitant to extra-oral features. In lack of any known medical background, the term "oral psoriasiform mucositis" is suggested.

Acantholytic squamous cell carcinoma (ASCC) is an uncommon variant of squamous cell carcinoma (SCC). It is characterized by a combination of typical SCC and pseudoglandular structures, dyskeratotic cells and prominent acantholysis. The purpose of this study was to analyze the histochemical and immunohistochemical characteristics of the intraoral variant of ASCC. Cases of intraoral ASCC were retrieved from the English language literature. Four new cases from our files were added. In total, 35 cases were included and analyzed in this study. The mean age of the patients was 61.5 + 13 years (age range 38–92 years), with a male-to-female ratio of 1.7:1. According to the available data, histochemical and immunohistochemical stains for mucins were found to be consistently negative. E- cadherin, a marker of adherens junctions, was usually reported to be expressed in areas of “typical” (non acantholytic) SCC, but reduced in the acantholytic areas. We examined for the first time the expression of claudin 1, a marker of tight junctions, and found it to be reduced in the acantholytic areas, similar to E-cadherin. Several cases of oral ASCC also expressed vimentin and cytokeratin (CK) 19, markers associated with epithelial-mesenchymal transition. A wide range of non-epithelial markers yielded negative immunoreactions. In conclusion, ASCC is an uncommon variant of squamous cell carcinoma. The acantholytic process appears to involve reduced expression of molecular components of both adherens junctions and tight junctions. These findings could suggest a relation to the epithelial mesenchymal transition process and therefore further studies are needed in order to establish such a link and the subsequent possible impact on the clinical outcome of the patients.

Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE) is a rare oral ulcerated lesion of uncertain etiology, showing eosinophil-rich granulation tissue, with occasional large atypical CD30 positive mononuclear cells. It had been suggested that it may represent an oral counterpart of cutaneous lymphomatoid papulosis, with a potential to evolve into CD30 + T cell lymphoma OBJECTIVES: To compare TUGSE and non-specific oral ulcers (NSU) clinically, histopathologically and by clonality analysis for T-cell receptor re-arrangement, aiming to determine whether TGUSE with atypical cells is a lymphomatous premalignant condition, and whether therapeutic approach should be radical or conservative.Retrospective archival analysis included 17 TUGSE and 8 NSU cases. Histopathological parameters included mean eosinophil number per high power field (HPF), presence of infiltration of deep soft tissues and presence of atypical cells. Immuno-morphometry comprised of the mean number of CD30+ atypical cells per HPF. T-cell receptor (TCR) gene rearrangement by polymerase chain reaction (PCR) was performed in all cases showing atypical cells. Clinical and follow up data were retrieved from files.TUGSE showed a significantly higher mean eosinophil number/HPF in comparison to NSU (7.0 + 4.2 cells and 2.3 + 1.72, respectively; p 0.001). Atypical cells were found in 9 (53%) cases of TUGSE and in only 1 (11%) case of NSU. CD30+ atypical cells were found in 7 (41%) cases of TUGSE and only in 1 (11%) case of NSU. Mean number of CD30+ cells/HPF was 0.23 + 0.19 (range 0 - 0.54 cells/HPF) for TUGSE. In the only NSU case with CD30+ cells, their density was 0.52/HPF. All lesions with atypical cells were polyclonal for TCR. All cases were self-limiting, with no recurrences, after 3-9 years (mean 4.6 years) follow up.Analysis found no support to the suggestion that TUGSE with atypical cells represents the oral counterpart of lymphomatoid papulosis or predisposes the lesions for a hematolymphoid malignancy. Suggestions for radical therapeutic approach and long-term follow-up are probably unjustified, with no recurrences or malignancy recorded following conservative treatment alone for a period of up to 9 years of follow-up. Staining for CD30 and PCR for TCR gene rearrangement should be reserved only for rare cases with abundant large atypical cells and/or unusual clinical behavior.

Aim To perform clinico-pathological characterization of a large series of oral metastases, collected from 3 main medical centers in Israel and compare findings to data on frequency of primary cancer types in the population. Materials Pathology archives were searched for cases of metastatic tumors to the oral soft tissues and jawbones, 1990 – 2016. Metastases to the skin of face or to major salivary glands have been excluded. Demographic data and histopathological features were analyzed. Results Study population included 60 patients, 35 females and 25 males (ratio of 1.4:1). The age range was 17–87 years, mean 67.7 + 14.36 years. Only 3 (5%) patients were under 40 years, the remaining clustered predominantly in the 60–80 year age group. The mean age of females (59 + 13.84) was significantly lower than that of males (67.44 + 14) (p = 0.03). There was an almost equal distribution between the oral soft tissue and the jawbones (48.3% and 51.7%, respectively). The five most common organs from which metastases were distributed to the oral cavity and jawbones combined were kidney (20%), breast (15%), cutaneous (predominately melanoma, 13%), lung (11.7%) and soft tissue-sarcomas (8.3%). For comparison, Israel National Cancer Registry 2013 reported that the most frequent malignancies were breast (25.8%), colorectal cancer (16.3%), lung (12%) and prostate (10%). Malignant melanoma was 6th (5.4%), kidney malignancy was only 9th in frequency (4.2%). Although the gingiva and jawbones were the most frequent locations, some cases presented in unusual locations, (mandibular vestibule, lower lip, posterior dorsal tongue), without any specific clinical feature to suggest metastasis. Conclusions The most frequent primary origins for oral metastasis do not correspond to the relative frequency of the primary tumors in the population, indicating that metastatic spread is not a random process. Although the majority of metastasis involves the gingiva and jawbones, any other oral mucosal location might be involved. Thus, in adult/older patients, metastasis from a distant site should be included in the differential diagnosis of oral masses at any oral location, whether the existence of a primary tumor is reported or not.

We aimed to immunohistochemically characterize the pattern of expression of epithelial markers in rare head and neck squamous cell carcinoma (HNSCC) variants: carcinoma cuniculatum (CC) and adenosquamous carcinoma (ASC). We also present an additional variant of HNSCC with concomitant basaloid and squamous components that has overlapping morphological features with odontogenic and non-odontogenic tumors, which we termed basalo-squamous carcinoma (BSC). The selected markers included CK5/6, p40, CK19, BerEP4, p16 and SOX10. All tumors were CK5/6 and p40 positive. CK19 and BerEP4 were positive in BSC and focally in ASC but negative in CC. p16 was positive in 3 (60%) of the CCs, focally positive in ASC and negative in BSC. SOX10 was negative in all three variants. Our results highlight the plasticity of the lining epithelium revealing differential profiles of immuno-expression of the selected molecular markers, possibly reflecting their diverse histopathogenesis.

Purpose To describe new cases of primary malignancy arising around dental implants. Materials and Methods Three patients presented with asymptomatic lesions around longstanding dental implants that resembled peri-implantitis. One case was primary large B-cell lymphoma and the remaining cases were primary squamous cell carcinoma in patients with oral lichen planus. The literature was reviewed for cases mimicking peri-implantitis. Results Of 42 implant-associated malignancies reported from 2000 through 2014, 85.7% were squamous cell carcinoma (69% primary and 9.4% metastatic). Most patients presented with pre-existing risk factors for oral cancer. Lymphoma was not associated with dental implants. Conclusions Primary and metastatic malignancies can occur in peri-implant mucosa, often with clinical and radiographic features resembling peri-implantitis. Clinicians should have a high index of suspicion for changes in peri-implant mucosa in patients with existing risk factors; however, rare cases such as lymphoma might present outside this risk population. Histopathologic analysis should be included in the management of selected peri-implant lesions to avoid delayed diagnosis of malignancy.

The purpose of this study was to compare the histopathological parameters of chronic/suppurative osteomyelitis, medication-related osteonecrosis of the jaw (MRONJ), and osteoradionecrosis (ORN), and to examine the hypothesis that distinct histological features can be related to a specific disease, allowing for diagnosis based on microscopic evaluation alone. One hundred and ten samples were reviewed by two examiners in a blinded fashion, and a semi-quantitative histomorphometric analysis was performed. The parameters evaluated included the presence or absence of necrotic bone, inflammation, reactive bone formation, bacteria, and osteoclasts. No statistically significant differences were found between groups for any parameter. Necrotic bone was common to all three diagnoses. Inflammation and reactive bone formation were present in all three diagnoses. The presence of bacteria was a prominent feature in all cases. Osteoclasts were scarce in MRONJ and osteomyelitis, and non-existent in ORN. The results of this study failed to identify distinctive microscopic characteristics in any of the three entities that could be used to differentiate between them. Therefore, it is impossible to reach a specific final diagnosis based on microscopic findings alone. The role of microscopic analysis is to serve as an aid to diagnosis that must be complemented by the patient's history and imaging.

Background Oral lichen planus (OLP) carries an increased risk for malignant transformation with aneuploid cells (ACs) being found in brush samples of a quarter of patients with OLP. Methods Patients with OLP were followed and repeated brush samples were simultaneously analyzed for morphology and fluorescent in situ hybridization (FISH) using centromeric probes for chromosomes 2 and 8. Results. Three patients with a high proportion of ACs developed oral cancer. Fifteen patients had ≥1% ACs (13 in affected sites and 2 in nonaffected sites), whereas only 2 of the 15 patients with

Purpose To evaluate the efficiency of decompression in treating odontogenic cystic lesions of the jaws in children. Materials and Methods All consecutive odontogenic cysts occurring in children and treated by decompression from 1994 to 2009 at 1 maxillofacial center were included in the present study. Clinical data included age, gender, jaw, histopathologic diagnosis, and decompression time. Radiologic data from panoramic radiographs before and after decompression included tooth involvement, locularity, location, involvement of adjacent vital anatomic structures, and cyst area. Results Thirty-two odontogenic cystic lesions from 26 children (14 boys [53.8%] and 12 girls [46.2%]) treated with decompression were included. The average age at the time of presentation was 11.6 ± 3.3 years (range, 7 to 18 yr). The mandible was involved in 13 cases (40.6%) and the maxilla in 19 (59.4%). All cysts were unilocular at presentation. Twenty-seven cysts (84.4%) showed tooth involvement. The diagnoses consisted of dentigerous cysts (20 [62.5%]), keratocysts (9 [28.1%]), and radicular cysts (3 [9.4%]). The mean decompression period was 7.45 ± 2.6 months (2 to 14 months). The mean standard lesion area index changed from 12.7 ± 0.9 mm 2 (3.6 to 44 mm 2 ) before compression to 2.3 ± 4.3 mm 2 (0 to 22.3 mm 2 ) after decompression. The mean percentage of reduction (POR) was 82 ± 16% (49 to 100%). The POR was ranked as good in 22 lesions (69%), moderate in 9 lesions (28%), and poor in 1 lesion (3%). Surgery was performed for 15 lesions (47%). Conclusion Decompression results in good regeneration potential of the bone in the developing craniofacial skeleton of children. Children might benefit from a less invasive surgical protocol.

Purpose We sought to study the spectrum of oral pathologies presenting clinically with papillary-verrucous features. Materials and Methods A 10-year (2007 to 2016) retrospective study of oral papillary lesions was undertaken. All biopsy reports that included a clinical description of papillary or verrucous architecture were retrieved. The data collected included clinical features, size, color, location, histopathologic diagnosis, age, and gender. Results The study included 137 patients, with a total of 150 lesions. The ages ranged from 10 weeks to 84 years (mean, 49 years). Histopathologically, 60% of cases were human papillomavirus (HPV) related, 19% showed hyperplasia, 11% had hyperplastic candidiasis, 7% were dysplastic or malignant, and 3% were benign of unknown etiology. Among the 7% of lesions diagnosed with dysplasia or malignancy, only 60% were suspected to have malignancy at the time of biopsy. HPV-related lesions and hyperplasia were most frequently found on the tongue (38% and 41%, respectively) and soft palate (21% and 14%, respectively). Hyperplastic candidiasis was most frequently found on the buccal mucosa and tongue (35% and 24%, respectively). Squamous cell carcinoma was found in 1.3% of total lesions and verrucous carcinoma in 1.3%. Of the verrucous or papillary malignant lesions, 50% were found on the gingiva. Most malignant lesions occurred in the 40- to 60-year age group. Conclusions The results of this study suggest that, because of the wide spectrum of entities presenting clinically with a papillary-verrucous architecture, biopsy is necessary for diagnosis. The clinical presentation allowed for overall accurate diagnosis in only 47% of cases and 60% accuracy in dysplastic or malignant cases. It is of considerable importance to correctly identify those lesions that are HPV related but at the same time to rule out those lesions that are unrelated to HPV to help alleviate a patient's anxiety. Most important, biopsy is mandatory for the recognition of malignant lesions with a papillary-verrucous architecture, which may mimic other benign entities in the group of papillary-verrucous lesions.

Metastatic dissemination to the oral cavity is rare and is usually the evidence of a wide spread disease with an average survival rate of 7 months. In almost a quarter of the cases, oral metastasis was found to be the first indication of an occult malignancy at a distant site. Metastatic lesions can be found anywhere in the oral cavity, however, the jaw bones with the molar area is the most frequently involved site. In the oral soft tissues, the gingiva is the most common site, suggesting the possible role of inflammation in the attraction of metastatic deposits. The most common primary malignancies presenting oral metastases were the lung, kidney, liver, and prostate for men, and breast, female genital organs, kidney, and colo-rectum for women. Most patients with jawbone metastasis complain of swelling, pain, and paresthesia. An exophytic lesion is the most common clinical presentation of metastatic lesions in the oral soft tissues. Early lesions, mainly those located in the gingiva, may resemble a hyperplastic or reactive lesion. Once a lesion is recognized as metastasis, the primary tumor site should be identified following clinical, radiological and histopathological investigations. If standardized diagnostic workup fails to detect the site of origin, then the term carcinoma of unknown primary is applied. Personalized medicine tools such as tissue-of-origin assays should be applied, either by immunohistochemical testing or by molecular-profiling methods as these may lead to a more favorable outcome.

Gingiva that is prone to inflammation may serve as a pre-metastatic niche for the attraction of circulating malignant cells. The aim of this study is to analyze cases of metastatic lesions to the gingiva compared with cases metastasizing to other oral mucosal sites. The pathogenesis of gingival metastases is discussed, with emphasis on the role of inflammation.The English-language literature between 1916 and 2011 was searched for cases of metastatic lesions to the oral mucosa; only cases metastasizing in the oral mucosa, gingiva, and periodontium were included.Two hundred seven cases were included. The gingiva was the most common site (60.4%), followed by tongue and tonsil. The most common primary sites were lung (24.2%), kidney (13.5%), skin (10.6%), and breast (8.7%). In 27%, the oral lesion was the first sign of a malignant disease. In most cases, the lesion appeared as an exophytic mass (96%) diagnosed clinically as a reactive gingival lesion. The presence of teeth was significantly associated with the development of gingival metastases: in 108 of 125 gingival metastases, the lesion was found adjacent to teeth (P0.001; odds ratio = 8.2). The average life expectancy after diagnosis of the metastasis was 3.7 months.The gingiva is the most common site for metastases to oral soft tissues, with strong association with the presence of teeth. This finding may be related to the role of inflammation in the attraction of metastatic cells to chronically inflamed gingiva.

Aim To investigate clinico-pathological features of lymphoma of the lips, and review the literature. Materials and Methods Retrospective analysis and review of English literature, 1996-2016. Results Analysis included 23 cases, 7 new cases and 16 from literature, 12 M: 11 F, age 7–82 years. Four occurred in children, mean age 10.1; 19 in adults, mean 61.1 years. The lower lip was involved in the majority of cases (16, 69.56%). 14 (60.87%) were isolated to the lips, 8 (34.78%) were multifocal. Nine (39.13%) occurred in association with Sjogren's syndrome, of which one also had Hashimoto thyroiditis. IgG4-related disease and HIV were reported in one case each. The lip salivary glands were involved in most cases (19, 82.6%); 3 (13.6%) showed only cutaneous involvement. The typical presentation was single or multiple nodules (15, 65.21%), with surface ulceration in only two (8.69%). Constituent symptoms were absent in all cases, paresthesia was reported in one (4.34%). The majority (18, 78.26%) was extranodal marginal zone B-cell lymphoma - mucosa-associated lymphoid tissue lymphoma (EMZB-MALT), and one case each was mantle cell, NK-T cell, CD30 positive and plasmablastic lymphoma. Conclusion The lips seem to have a unique pattern of non-Hodgkin lymphoma dominated by EMZB-MALT lymphoma, rarely other types. In more than half, neither Sjogren's syndrome nor other chronic inflammation was identified. Lesions tend to present as asymptomatic slowly progressing, non-ulcerated submucosal masses. Lymphoma should be considered even in the absence of constituent symptoms, as most cases showed none. Although the number of reported cases is rather small, disease course is usually prolonged and prognosis seems to be good.

Purpose: This study is a histopathological analysis of lesions clinically diagnosed as peri-implantitis (PI). Materials and Methods: This retrospective study included microscopic findings in 117 peri-implant biopsies from lesionspresenting clinical and radiographic features of peri-implantitis. Results: The study group included 117 biopsies, mean age 55.2 years; 60.9% of biopsies were from failing implants duringexplantation, the remaining from surviving implants. All cases showed microscopic evidence for inflammation; however,although 41% exhibited only nonspecific inflammation, 29.9% exhibited actinomyces-related inflammation, 18.8% pyo-genic granuloma (PG), and 10.3% giant cell granuloma (GCG). Differences in implant failure rates between pathologicaldiagnostic groups were not statistically significant. Lesions with simple inflammation could not be distinguished clinicallyor radiographically from the potentially destructive lesions. Conclusions: There were no clinical features which could distinguish PI with simple inflammation from potentiallydestructive lesions mimicking PI, such as GCG, PG, and actinomycosis. However, to control GCG and PG surgicalprocedures would be recommended, actinomycosis would indicate specific antibiotics, whereas in nonspecific inflamma-tion, these measures may not be indicated. The results of the present study provide evidence for the importance of earlymicroscopic examination of lesions presenting clinically as peri-implantitis, a step toward more accurate diagnosis andimproved treatment of PI and lesions mimicking PI.KEY WORDS: actinomyces, giant-cell-granuloma, inflammation, peri-implantitis

Objectives Necrotizing sialometaplasia (NS) is an uncommon reactive lesion involving the minor salivary glands. This study aimed to investigate the expression of hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor (VEGF), and epithelial growth factor receptor (EGFR) in the pathogenesis of NS. Methods Paraffin-embedded tissue sections from 10 cases of NS were immunohistochemically stained for HIF-1α, VEGF, and EGFR. A semiquantitative morphometric analysis was performed and compared with normal palatal salivary glands and traumatic ulcerations. Results Hypoxia-inducible factor alpha staining was observed in most elements of the affected area, the acini and ducts of the involved salivary glands as well as in the inflammatory infiltrate, the endothelial cells, and stromal cells. HIF-1α was almost absent in the control glands (P

Purpose To evaluate the clinical appearance and rate of ulceration of oral mucosal malignancies, and to investigate the accuracy of clinical provisional diagnoses. Methods A 10-year retrospective analysis, which included diagnostic biopsies of malignant tumors of the oral mucosa. The clinical provisional diagnoses were compared with final diagnoses. Results Two hundred and twenty-seven oral mucosal malignant tumors were included. Squamous cell carcinoma and its variants accounted for the majority (78%) of all malignant tumors. The most common clinical presentations were non-ulcerated (59.7%) and ulcerated masses (20.4%). Only 11.9% presented as indurate ulcers. The highest ulceration rate of all malignancies was recorded for SCC, with only about half of SCC and its variants ulcerated at the time of biopsy. 31.1% of all malignancies were not clinically suspected to be malignant and did not even include a request to rule out malignancy. There was a better agreement between the clinical provisional diagnoses and microscopic diagnoses in the SCC group than in other types of malignancy (P

Objectives Clinico-pathological evaluation of bisphosphonate (BP)-related osteonecrosis of jaws, comparison between oral (PO) and intravenous (IV) BPs and histomorphometric analysis of associated actinomyces . Study design Retrospective clinical and histomorphometric analysis. Data on background, clinical, treatment and follow-up were analyzed. Actinomyces colonies were identified by typical filamentous colony morphology, Gram, and PAS stains. Colony density and relative colony surface area were measured. Results Fifty-two patients were included, 37 (71.2%) IV, 15 (28.8%) PO BPs. with a mean duration of 2.33 and, 4.33 years respectively. One hundred percent of cases exhibited actinomyces colonization. The relative colony surface area was significantly higher in PO treatment ( P = .024), with no differences in density, healing time or antibiotic treatment periods. High frequency of diabetes mellitus (60% PO cases) and corticosteroid treatment (25% of cases) were recorded. Conclusion Infection with actinomyces is a common denominator in BP-related osteonecrosis of the jaws (BRONJ), regardless of administration route. Diabetes and corticosteroid treatment seem to be important contributing factors for BRONJ.

Objective The aim of this study was to describe a new case series of peri-implant malignancy, review the literature, and discuss the implications of malignancies resembling peri-implantitis. Study Design This study was a retrospective analysis of cases from 2000 to 2016. Results Seven patients (two males and five females), aged 44 to 89 years, were included, representing 1.5% of oral malignancy cases. Five cases were squamous carcinoma, one of basal cell carcinoma, and one of carcinoma of metastatic origin. Six cases presented with nonulcerated overgrowth, with bone loss in three and massive osteolysis in one. Misinterpretation as peri-implantitis delayed diagnosis in six cases. Risk factors included previous oral malignancy (2), potentially malignant conditions (2), and smoking (1). Of the 47 cases in the English language literature, 85% were squamous cell carcinoma and 8.5% had distant metastasis. Most cases had one or more risk factors. Conclusions Peri-implant malignancy may represent up to 1.5% of oral malignancy cases. Clinical features imitating peri-implantitis may delay diagnosis. Lesions failing to respond to treatment, especially in patients with pre-existing risk factors, should significantly increase suspicion. Histopathology is crucial for diagnosis.

To compare the spectrum of pathologies in ulcerated versus non-ulcerated exophytic oral mucosal lesions and explore the significance of surface ulceration as an indication of malignancy. Retrospective analysis of exophytic lesions of the oral mucosa, 2009–2011. 713 biopsies of exophytic lesions of oral mucosa were included, of which 9.4 % were ulcerated. Significant differences were found between ulcerated and non-ulcerated lesions. Of the ulcerated lesions 67.2 % were reactive, 31.3 % malignant and 1.5 % benign, compared to 86, 8.4 and 5.6 % respectively in non-ulcerated lesions (p

Nodular fasciitis is a benign non-neoplastic myofibroblastic proliferation, involving the head in 7% to 20% of cases. Intravascular fasciitis (IVF) is a rare variant, with a unique intravascular growth pattern. Only 4 maxillofacial cases have been previously reported. We describe a 58-year-old woman with a rapidly growing, hard, mobile buccal submucosal swelling. CT scans identified a well-defined, 1.7-cm isodense lesion, located between the mental foramen and masseter muscle, which was excised under general anesthesia. A well-defined cellular nodular mass was composed of bland spindle cells, in a densely vascularized, focally myxoid matrix, involving an arterial lumen, and extending into adjacent tissues. Mitoses were rare. Immunohistochemistry was positive for smooth muscle actin, negative for keratins, S-100, epithelial membrane antigen, caldesmon, p53 and Alk. CD31 and CD34 were positive only in the vascular component, supporting the diagnosis of intravascular fasciitis.

Odontogenic keratocyst (OKC), which was originally described by Philipsen 1 in 1956, has distinctive clinical and histologic characteristics. The histologic features of OKC include a thin epithelial lining of uniform thickness, with palisading of basal cells and a thin corrugated layer of parakeratin. OKCs have a high recurrence rate, which can be attributed both to the high proliferative activity of the epithelial lining and to the extension along the bony cancellous spaces, which makes complete enucleation difficult. 2,3 In a recent report that reviewed hundreds of published cases, the recurrence rates ranged from 0% to 100%, with those undergoing with enucleation having the worst recurrence rates (0% to 56%), in contrast to those undergoing resection, with a recurrence rate of 0% in all reviewed series. The investigators explained this discrepancy by the differences in the length of the postoperative follow-up periods, operative techniques used, differences in cyst location, the presence or absence of infection, associated teeth, involvement of mucosa, lesion size, or inclusion of cases with Nevoid basal cell carcinoma syndrome. 4 In the 2005 edition of the World Health Organization Classification of the Head and Neck Tumors, the odontogenic keratocyst was reclassified from a cystic to a neoplastic lesion, and the term “keratocystic odontogenic tumor” (KCOT) was coined. 5 In very rare cases, KCOT has been described as a solid, rather than a cystic, lesion. Only 3 cases of solid KCOT have been previously reported; thus, information on its characteristics is minimal. However, it has been suggested in 2 of these reports that these solid variants might be clinically more aggressive than the more common cystic variant of KCOT. 6,7 Keratoameloblastoma is another rare odontogenic tumor, with microscopic features of both ameloblastoma and KCOT, 8 which bears significant overlap with features of solid KCOT, and should be considered in the differential diagnosis. The purpose of the present report is to present a case of solid KCOT that did not present with unusually aggressive behavior and to discuss in detail the histologic differential diagnosis with keratoameloblastoma.

To evaluate disease dynamics, treatment results, and frequency of malignant transformation. Ten-year single center retrospective study. The study included 171 patients, 28–99 years old. Follow-up was 1–16 years. 49.5% exhibited changes in clinical presentation, with 19% yearly increase of probability for type shift. Index of extent (number of oral locations) showed a mean 40% decrease and 94.1% reported improvement. There were significant differences between treated and untreated patients (P = 0.012). Patients with or without systemic diseases had identical treatment requirements for oral lesions. The prevalence of SCC was 5.8%. Oral lichen planus constantly changes presentation and extent of involvement. The effect of systemic diseases was insignificant in the present study. There is a clear value for treatment to reduce the extent of lesions. The results indicate that all clinical forms of the disease need to be equally followed since the clinical presentation typically changes over time, while malignant transformation can occur in all forms.

BACKGROUND: Neurovascular hamartoma (NVH), in particular in the oral cavity, is rarely described in the literature. The low number of cases may reflect a genuine rarity of the lesion, or it may be due to its being unrecognized and ⁄or under-reported. OBJECTIVES: To investigate clinical and microscopic features of oral NVH and to define microscopic diagnostic criteria with emphasis on the differential diagnosis. METHODS: Archival cases diagnosed as oral NVH between 1999 and 2011 were retrieved; clinical and demographic data were collected, and a paired morphometric analysis was conducted, with each case of NVH a case of fibrous hyperplasia (FH) from the same oral location. The nerve bundle and blood vessel density were quantified in five microscopic fields at ·100 magnification. RESULTS: The study group included 25 oral NVH, 11 men and 14 women, aged 6‐76 years, (mean 44). The majority occurred in the tongue (54%), followed by the buccal mucosa and lower lip (17% each), clinically presenting as asymptomatic 0.25‐2.5 cm exophytic masses. Microscopic characteristics included poorly circumscribed masses of closely packed nerve bundles and blood vessels in a loose matrix, containing minimal or no inflammation. The mean nerve bundle density was significantly higher in NVH (4.28 ± 1.26) in comparison with FH (0.27 ± 0.27), (P < 0.00001), and mean vessel density was significantly lower (5.98 ± 1.4 vs. 7.8 ± 1.9, respectively), (P < 0.0003). CONCLUSION: Oral NVH may not be as rare as previously considered. Morphometric analysis demonstrated that NVH presents a separate distinct entity. J Oral Pathol Med (2012) 41: 348–353