[A Case of Severe Skin Disorder during Pembrolizumab Treatment for Recurrent Maxillary Gingival Carcinoma].

Immune checkpoint inhibitors are known to produce immune-related adverse events(irAE)that require medical management. Herein, we report a case of a patient treated with pembrolizumab who experienced a Grade 3 interrupted skin disorder. The patient is a 67-year-old female diagnosed with right maxillary gingival squamous cell carcinoma(cT4aN0M0, Stage ⅣA)and underwent partial right maxillectomy, right extended supra-omohyoid neck dissection, and maxillary reconstruction using a forearm flap. Six months postoperatively, late lymph node metastases with extracapsular spread was found in the right buccal lymph node and the left neck, and the patient underwent right buccal lymphadenectomy and left modified radical neck dissection. After postoperative combined chemoradiotherapy(cisplatin plus IMRT)followed by 13 courses of cetuximab plus paclitaxel, a recurrent lesion was found in the right buccal region. After 8 courses of pembrolizumab, a skin rash appeared on the forearm, chest, and back, which was diagnosed as Grade 3 irAE, requiring hospitalization. The patient was re-instituted after waiting for improvement of the skin disorder. The pembrolizumab at 75% reduction dose was re-administrated, and the patient has been followed up so far.

Metastatic mucinous adenocarcinoma from breast mimicking a pyogenic granuloma in the gingiva: a case report.

Mucin-producing adenocarcinomas (MAC) are an extremely rare, indistinct group of neoplasm having either a salivary gland origin or with prominent glandular component. The diagnosis is chiefly based on the histological aspect conjoined with immunohistochemical evaluation as clinico-radiographical features are non-specific. It can arise as a primary metastasis to soft tissues, most commonly from either lung, breast, kidney, or colon. This paper reports a 51-year-old woman with buccolingual gingival swelling having a final diagnosis of metastatic mucinous adenocarcinoma from the breast. A tissue biopsy was performed followed by immunohistochemistry that confirmed the diagnosis. They are extremely rare, making the diagnosis challenging as it may mimic a benign neoplasm. It accounts for approximately 1% of all oral malignant neoplasms having gingival propensity. The clinician should therefore take into account every diagnostic aspect while encountering such oral lesions to achieve proper patient welfare.

Role of collagen and immunostaining for TGF-ß in the clinical and microscopic findings of pyogenic granuloma and peripheral ossifying fibroma.

BACKGROUND: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-ß) in the clinical and microscopic findings of PG and POF. MATERIAL AND METHODS: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-ß) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0). RESULTS: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-ß+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-ß suffered from modifications by the time of evolution and the size of the lesion. CONCLUSIONS: Although PG and POF are reactive gingival lesions, the expression of TGF-ß and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components.

A Periodontal Perspective on the Successful Treatment of Recurrent Benign Gingival Lesions Affecting the Anterior Dentition: Two Case Reports.

Recurrent benign gingival lesions occurring in the anterior dentition are clinical dilemmas. While complete removal of such lesions is required to prevent recurrence, this can result in a poor esthetic outcome. Relative to this conundrum, this report discusses the diagnosis, psychologic management, and clinical treatment of two patients with recurring lesions on the facial gingiva of the mandibular and maxillary incisors, respectively. Patient A, a 55-year-old woman, presented with a recurrent peripheral ossifying fibroma (POF); Patient B, a 76-year-old man, presented with a recurrent pyogenic granuloma (PG). Both patients underwent multiple procedures and were ultimately treated without lesion recurrence. The efficacious surgical treatment of recurrent gingival lesions like POF and PG requires an aggressive approach involving lesion removal of the lesion as well as a 1.0- to 2.0-mm margin of normal tissue, underlying alveolar bone, and associated periodontal ligament (PDL). The rationale for this approach stresses the potential periodontal and esthetic ramifications that were considered. In summary, when recurrent benign gingival lesions are localized to the anterior part of the mouth, the approach to their surgical removal should be modified to minimize the extent of gingival recession and other potential esthetic issues.

Preserving periodontal tissue in the treatment of a large peripheral ossifying fibroma: a case study.

Peripheral ossifying fibroma (POF) is a reactive, benign gingival enlargement. Its etiology is not fully known. It can be seen in many different sizes in the mouth. The histopathological appearance of POF is mineralized tissue and fibrous proliferation. All relevant soft and hard tissues must be removed to prevent recurrence. Periodontal tissue remaining after excision is important for tooth preservation. With large lesions, the loss of healthy periodontal tissue is also large. Periodontal surgical approaches are important to preserve the remaining periodontal tissue. The positive effects of autogenously obtained titanium-prepared platelet-rich fibrin (T-PRF) and connective tissue graft (CTG) on soft tissue are well known. A 34-year-old woman presented with a fibrous and pedunculated gingival mass in the upper left canine premolar region. The operation was performed with complete excision of the lesion down to the bone along with the surrounding healthy tissue. Periodontal treatment of the large defect created after excision of a large POF lesion was performed with laterally positioned flap, CTG and T-PRF. The periodontal tissue and defect were noted to heal in a healthy manner at the 6-month follow-up. POF is a benign lesion; however, it has a high recurrence rate. Complete elimination of the lesion is crucial to prevent recurrence. Periodontal surgical methods and biomaterials applied after surgical excision are significant to maintain the periodontal health of the remaining teeth and tissues.

Neonatal alveolar lymphangioma: A rare benign oral disease case report and literature review.

BACKGROUND: Neonatal alveolar lymphangioma (NAL) is a rare benign condition most often reported in the oral cavity of neonates of African descent. CASE DESCRIPTION: The authors present a case report of bilateral NAL, including follow-up images at 6 months and 17 months. The clinical differential diagnosis includes dental lamina cyst, hemangioma, congenital epulis of the neonate, and melanotic neuroectodermal tumor of infancy. Key differences to assist in making the distinction are described. PRACTICAL IMPLICATIONS: The distinguishing characteristics of NAL make a clinical diagnosis possible. Accurate clinical recognition of NAL is essential because biopsy is not typically indicated. Because this is a clinical diagnosis, follow-up for 1 year or until complete resolution; biopsy is suggested if clinically indicated for residual or recurrent lesion.

A case of synchronous double cancers consisting of maxillary gingival carcinoma and intraductal papillary mucinous carcinoma, invasive: case report.

BACKGROUND: The development of synchronous multiple primary cancers is one of the major causes of death in patients with head and neck cancer. Herein, we report a case of synchronous intraductal papillary mucinous carcinoma (IPMC), invasive in a patient with maxillary gingival carcinoma. CASE PRESENTATION: A 73-year-old female visited our hospital complaining of a mass on the left side of the maxillary gingiva. Intraorally, an exophytic tumor, 50 × 25 mm in size, was found on the gingiva of the left maxillary posterior, and a diagnosis of squamous cell carcinoma was revealed by cytology. Emission tomography/ computed tomography with 18 Fluorodeoxyglucose-Positron (18FDG- PET/ CT) showed increased accumulation in the left maxillary gingiva, the left side of cervical lymph nodes, and the main pancreatic duct. The pancreatic ductal tumor was performed the biopsy at esophagogastroduodenoscopy (EGD) and resulted in a pathological diagnosis of IPMC, invasive. The patient was diagnosed as synchronous double primary cancers consisting of maxillary gingival carcinoma cT4aN2bM0 and IPMC, invasive cT3N0M0. She refused radical treatment, and died 11 months later. CONCLUSION: 18FDG- PET/ CT, EGD and multidisciplinary approach is required for the detection and determining the treatment strategy of synchronous double primary cancers.

[Clinical factors affecting the prognosis of lower gingival squamous cell carcinoma].

OBJECTIVE: To define the clinical factors that influence local recurrence and survival in patients with lower gingival squamous cell carcinoma (LGSCC) and determine whether bone invasion is an independent prognostic factor for them. METHODS: A total of 104 patients with LGSCC hospitalized in Peking University Stomatology Hospital from June 2013 to December 2015 were enrolled in this retrospective study.All the patients were followed-up for more than 3 years.The degree of bone invasion was assessed using preoperative imaging data (CT and panoramic radiograph).The degree of bone invasion was divi-ded into four categories: no bone invasion, invasion of cortical bone, invasion of bone marrow cavity, and invasion of the mandibular canal.According to the central position of tumor, it was divided into two types: anterior mandibular invasion (anterior region of the mental foramen) and posterior mandibular invasion (posterior region of the mental foramen). RESULTS: of different invasion depth groups were compared using Mann-Whitney U test.P value < 0.05 was considered to be statistically significant.Kaplan-Meier survival analysis method was used to draw survival curve, and COX regression was used to explore the risk ratio (HR) and 95% confidence interval (CI) of prognostic factors of LGSCC. RESULTS: The follow-up results showed that the 1-, 3-, and 5-year survival rates of LGSCC in this group were 91%, 84%, 82%, respectively.32.7%(34/104) of patients had cervical lymph node metastasis.The cervical lymph node metastasis rate of the anterior segment of the mandible was 12.5%(2/16), and 36.4%(32/88) for the posterior segment of the mandible (P < 0.05).Univariate and multivariate COX analysis showed that the N stage and local recurrence were the prognostic factors of LGSCC patients (P < 0.05). CONCLUSION: As the degree of mandibular invasion increases, the prognosis of patients with mandibular gum cancer becomes worse.N stage and local recurrence are prognostic risk factors for LGSCC.The incidence of cervical lymph node metastasis for LGSCC is related to the primary tumor location.It is concluded that tumors located at the posterior of the mandible might be more prone to cervical lymph node metastasis than the anterior of the mandible.Thus various levels of cervical lymph node dissection strategies should be adopted for different sites of LGSCC.

Congenital Epulis: A Rare Head And Neck Tumor in the Newborn.

Congenital epulis is a rare tumor; when voluminous and ulcerated, appearance can generate concern. Nevertheless, it is a benign lesion that is easily treated with surgery. This is a retrospective study, with the presentation of 2 cases treated by the same team from 2016 to 2020 and a bibliographic review (PubMed and Elsiever). This surgical team is based in Buenos Aires, working in the private medical system. Congenital epulis is an infrequent, benign tumor affecting females predominantly, appearing at birth on the alveolar median ridge of the maxilla. Its pathogenesis is uncertain. Voluminous tumors interfere with feeding, but respiratory interference is exceptional. Histologically, this tumor is similar to the granular cell tumor but has different clinical characteristics and Periodic Acid Schiff stain. Prenatal diagnosis with ecographic or magnetic resonance imaging is ideal; if undiagnosed prenatally, clinical diagnosis is done based on typical features. Surgical excision is the treatment of choice.

Gingival neoplasms: a multicenter collaborative study of 888 patients in Brazil.

BACKGROUND: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. MATERIAL AND METHODS:  All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. RESULTS:  From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). CONCLUSIONS:  Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers.

A large-cohort study of 2971 cases of epulis: focusing on risk factors associated with recurrence.

BACKGROUND: To analyze the clinicopathological features of different histological subtypes of epulis, and evaluate the risk factors associated with recurrence. MATERIALS AND METHODS: A retrospective study including 2971 patients was performed. The patients' sex, age, location, size, histological subtypes, recurrence information, oral hygiene habits, periodontitis symptoms and smoking history were retrieved from the patient medical records and follow-up information. RESULTS: Among the 2971 cases, focal fibrous hyperplasia (FFH) was the most common lesion (60.92%), followed by peripheral ossifying fibroma (POF) (29.32%), pyogenic granuloma (PG) (8.08%) and peripheral giant cell granuloma (PGCG) (1.68%). The peak incidence of epulis was in the third and fourth decade of life, with a mean age of 45.55 years. Female predominance was found in all types of lesions with a female to male ratio of 1.71:1. PG had the highest recurrence rate (17.18%), followed by POF (12.98%), FFH (9.55%) and PGCG (8.82%). Histological subtypes were significantly correlated with the recurrence of epulis (P = 0.013). Regular supportive periodontal therapy (P = 0.050) had a negative correlation with recurrence, whereas symptoms of periodontitis (P < 0.001) had a positive correlation with the recurrence of epulis. CONCLUSIONS: Controlling the periodontal inflammation and regular supportive periodontal therapy might help reduce the recurrence of epulis.

Congenital Epulis Diagnosed Antenatally.

Background: Congenital epulis is a benign gingival tumor whose differential diagnosis includes other oral-facial masses such as teratoma, hemangioma, lymphatic malformation and dermoid cysts. This tumor can cause obstruction of the airway or feeding problems in the newborn. Surgical excision is the treatment of choice. Case Report: We present a case of congenital epulis, diagnosed prenatally with ultrasonography. Conclusion: Although difficult, a defined prenatal image of congenital epulis is possible by means of accurate high-resolution ultrasonography. It facilitates the narrowing down of differential diagnosis. The confirmatory final diagnosis relies on histopathological examination.

Gingival and alveolar mucosal reactive hyperplastic lesions: a retrospective clinical and histological study of 996 cases.

BACKGROUND: gingival/alveolar mucosal reactive hyperplastic lesions (GRHL), including fibrous hyperplasia (FH), pyogenic granuloma (PG), peripheral ossifying fibroma (POF) and peripheral giant cell lesion (PGCL), are a common group of oral diseases. The aim of the present study was to access the frequency and distribution of the clinical and histological features of these disorders in a Brazilian population. MATERIAL AND METHODS: all specimens diagnosed as GRHL in three Oral Pathology laboratories were selected for the study. Clinical information was retrieved from the laboratory biopsy forms and hematoxylin and eosin stained histological slides were reviewed for analysis of the histological characteristics. RESULTS: final sample was composed of 996 specimens, including 463 FH (47%), 280 PG (28%), 183 POF (18%) and 70 PGCL (7%). Females were more affected by FH, PG, and POF, and most cases affected adults with mean ages ranging from 40 to 53 years. FH, PG, and POF were more common in the upper gingiva/alveolar mucosa. Most PG, POF and PGCL were pedunculated, in contrast with FH (p<0.001). PG, FH and POF were mostly red or normal mucosal in color, while PGCL were mostly red/purple (p<0.001). PGCL were larger, followed by POF, FH and PG (p<0.001). Some histological features were characteristically found in some conditions, but they were also encountered in other lesions with variable frequencies. CONCLUSIONS: Oral medicine specialists, oral pathologists and periodontists are usually the professionals in contact with patients presenting GRHL and it is of upmost relevance that they should be familiarized with their clinical and histological profile.

Reconstruction of Anterior Mandibular Defect Using Submental Island Flap Pedicled With Mental Artery.

Gingival carcinoma is a common malignant tumor occurring in the anterior area of the mandible, which can be derived from the epithelium of gingival mucosa. Surgical extended resection is the main treatment of gingival cancer, which can lead to anterior mandibular defect including mouth floor and mandible and mucosa of lower lip. According to the size of the defect, the common repair method is free musculocutaneous flap with vascular pedicle or pedicle flap. We present a method of repairing mandibular anterior tooth defect with an island flap pedicled with the mental artery.

Oral Pathology in Portuguese Dogs: An Eight-Year Biopsy-Based Retrospective Study.

The oral cavity of the dog can be the site of several types of pathology including both benign and malignant lesions. The aim of this study was to analyze the frequency and clinical-pathological characteristics of oral lesions present in a cohort of Portuguese dogs. A retrospective observational cross-sectional study on 704 canine oral lesions submitted for histopathological diagnosis to a Veterinary Pathology Center in the north of Portugal from 2010 to 2017 was performed. Gender, age, location of the lesion and the histopathological diagnosis was analysed. From the 704 cases included, 307 (43.6%) were females and 397 (56.4%) males. The mean age was 9.53 ± 3.6 years-old (range 3 to 240 months). The site most frequently affected was the gingiva (n = 283; 40.2%). 342 (48.6%) cases were malignant neoplasms, most represented by oral melanoma (n = 129; 37.7%). 256 (36.4%) cases were benign neoplasms, most represented by fibromatous epulis of periodontal ligament origin/peripheral odontogenic fibroma (FEPLO/POF) (n = 208;81.3%). 106 (15%) were non-neoplastic lesions, most represented by gingival hyperplasia (n = 25, 23.6%). This study provides useful information about frequency and distribution of oral lesions in dogs over a period of eight years allowing valuable comparison with other countries and other species. The most common benign tumours were FEPLO/POF while oral melanoma was the most common malignant tumour.

Utilization of a nanostructured lipid carrier encapsulating pitavastatin-Pinus densiflora oil for enhancing cytotoxicity against the gingival carcinoma HGF-1 cell line.

Oral squamous cell carcinoma (OSCC) is the most common epithelial tumor of the oral cavity. Gingival tumors, a unique type of OSCC, account for 10% of these malignant tumors. The antineoplastic properties of statins, including pitavastatin (PV), and the essential oil of the Pinus densiflora leaf (Pd oil) have been adequately reported. The goal of this investigation was to develop nanostructured lipid carriers (NLCs) containing PV combined with Pd oil and to determine their cytotoxicity against the cell line of human gingival fibroblasts (HGF-1). A central composite quadratic design was adopted to optimize the nanocarriers. The particle size and stability index of the nano-formulations were measured to evaluate various characteristics. TEM analysis, the entrapment efficiency, dissolution efficiency, and the cytotoxic efficiency of the optimized PV-loaded nanostructured lipid carrier drug delivery system (PV-Pd-NLCs) were evaluated. Then, the optimal PV-Pd-NLCs was incorporated into a Carbopol 940® gel base and tested for its rheological features and its properties of release and cell viability. The optimized NLCs had a particle size of 98 nm and a stability index of 89%. The gel containing optimum PV-Pd-NLCs had reasonable dissolution efficiency and acceptable rheological behavior and acquired the best cytotoxic activity against HGF-1 cell line among all the formulations developed for the study. The in vitro cell viability studies revealed a synergistic effect between PV and Pd oil in the treatment of gingival cancer. These findings illustrated that the gel containing PV-Pd-NLCs could be beneficial in the local treatment of gingival cancer.

Immunohistochemical Characterization of Gingival Fibromas.

PURPOSE: Gingival fibromas (GFs) are fibrous lesions of the gingiva that are not well defined in the literature. They are histologically similar to peripheral ossifying fibromas (POFs), both being characterized as cellular proliferations of dense fibrous tissue, with POFs differing in that they demonstrate foci of calcification. This study aims to expand upon the immunohistochemical characterization of GFs, and to confirm their osteoblastic phenotype. METHODS: Formalin fixed, paraffin embedded GFs, POFs and fibroepithelial polyps (FEPs) of the gingiva were examined. Immunohistochemical staining was performed for special AT-rich sequence binding protein 2 (SATB2), runt-related transcription factor 2 (RUNX2), osteocalcin and alpha-smooth muscle actin (αSMA). Sections were evaluated by light microscopy and the immunohistochemical staining patterns were assigned immunoreactive scores (IRS) based on percentage of stained cells and intensity of staining. RESULTS: GFs, POFs, and FEPs of the gingiva expressed osteoblastic markers SATB2, RUNX2 and osteocalcin. GFs and POFs expressed αSMA while FEPs of the gingiva did not. GFs and POFs had similar staining patterns of SATB2, RUNX2 and αSMA. DISCUSSION: These findings demonstrate that GFs and POFs exhibit a similar immunohistochemical profile, and supports a theory that GFs are osteoblastic lesions possibly related to POFs.

[Two Cases of Advanced Lower Gingival Carcinoma Treated Surgically Using a Novel Patient-Specific Full Custom- Made Mandibular Reconstruction Plate System].

The treatment of advanced lower gingival carcinoma requires postoperative chemoradiotherapy; therefore, simultaneous hard-tissue reconstruction may not be indicated. In these cases, mandibular reconstruction is performed using a temporal reconstruction plate and various skin flaps. Herein, we reported 2 cases of advanced lower gingival carcinoma treated with a novel computer-assisted patient-specific, fully custom-made mandibular reconstruction plate system(Cosmofix®)in combination with a pedicle/free flap. In case 1, an 80-year-old female patient was diagnosed with right lower gingival carcinoma( cT4aN3bM0, Stage ⅣB). Under general anesthesia, she underwent tracheostomy, bilateral neck dissection, segmental mandibulectomy, and mandibular reconstruction using Cosmofix® in combination with an ulnar forearm free flap. In case 2, an 81-year-old male patient was diagnosed with right lower gingival carcinoma(cT4aN2bM0, Stage ⅣA). The patient underwent maintenance dialysis and required minimally invasive surgery using a pedicle flap. Under general anesthesia, the patient underwent tracheostomy, right modified radical neck dissection, segmental mandibulectomy, and mandibular reconstruction using Cosmofix® in combination with a pectoralis major myocutaneous flap. Postoperative facial morphology, occlusion, eating, swallowing, articulation, and other dysfunctions were minimal in both the cases. Adjuvant chemoradiotherapy was recommended. In conclusion, the utilization of the Cosmofix® system enabled both esthetic and functional reconstruction following segmental mandibulectomy for advanced lower gingival carcinoma.

Peripheral cemento-ossifying fibroma - A rare case report.

Peripheral cemento-ossifying fibroma (PCOF) is a relatively rare tumor classified between fibro-osseous lesions. PCOF is an osteogenic neoplasm that ordinarily presents as an epulis-like growth with uncertain pathogenesis. It predominantly affects young adults, with peak prevalence between the first and second decades of life. We present here the case report of a 15-year-old girl, which was previously surgically excised twice and had recurred both the times. The disease duration was 2 years and a follow-up of 1-year was done. Clinical, radiographic, and histological characteristics are discussed with recommendations regarding the treatment is provided.