Clinicopathological features of myofibromas and myofibromatosis affecting the oral and maxillofacial region: A systematic review.

BACKGROUND: Myofibromas are rare benign neoplasms composed of myoid cells and myofibroblasts. This study aimed to systematically review case reports and a series of myofibromas (MF) and myofibromatosis (MFT) occurring in the oral and maxillofacial regions in order to describe their main clinicopathological features. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches were conducted in 2023 in four databases: MEDLINE/PubMed, Web of Science, Scopus, and EMBASE. A manual search and a search in the grey literature were also conducted. The lesions were classified as MF or MFT according to their original report. RESULTS: A total of 169 cases were included in this systematic review. Men were slightly more affected, with a painless nodule. When occurring in soft tissue, MF usually developed in the gingiva (mean age:29.23 ± 21.93 years) and when it was intra-osseous, it occurred more frequently in the posterior mandible (mean age:14.33 ± 15.62 years). MFT occurred mainly in the mandible and was predominantly described as well-circumscribed masses of spindle cells organized in fascicles with a prominent vascular activity in a hemangiopericytoma-like pattern. The lesions were mainly positive for smooth muscle actin and vimentin immunomarkers. Surgical excision was the treatment of choice in the majority of cases and recurrence was observed in only three cases. CONCLUSION: MF and MFT affect more men, with an indolent clinical course. Intra-osseous tumors and MFT seem to occur more frequently in younger individuals. These lesions seem to have a good prognosis and low recurrence.

Clinicopathological Features of Metastasis to the Oral and Maxillofacial Region-Multicenter Study.

BACKGROUND: This study aimed to investigate the clinicopathological features of metastases in the oral and maxillofacial regions. METHODS: In this retrospective study, biopsy records were obtained from referral centers for oral and maxillofacial diagnosis in Brazil, Guatemala, Mexico, and South Africa. RESULTS: A total of 120 cases were evaluated. Of these, 53.78% affected female patients, with a mean age of 57.64 years. Intraosseous lesions were more frequent, particularly in the posterior region of the mandible (49.58%). Clinically, most cases presented with symptomatic swelling, with an average evolution time of 25 months. The clinical diagnostic hypothesis in most instances was that of a malignant lesion. Breast cancer was the most common primary tumor location in females, while lung origin was most common in males. In most cases, the primary cancer was an adenocarcinoma (44.73%). The follow-up period was available for 29 cases, and out of these, 20 had died due to the disease. CONCLUSION: Although this is a rare condition, clinicians should be aware that any oral lesions have the possibility of being metastatic, particularly in individuals with a previous history of cancer. The findings from this study could assist clinicians in prompt diagnosing these lesions and subsequent conducting oncologic assessments and treatment.

Synchronous odontogenic tumors: A systematic review.

This systematic review aimed to incorporate published information about synchronous odontogenic tumors (SOTs) with an analysis of the demographic and clinical characteristics from the cases published in the literature. Case reports and case series of SOT were searched in PubMed, Web of Science, Scopus, and EMBASE. A descriptive statistical analysis was performed. Twenty-eight studies comprising 30 cases of SOTs were included. Considering all cases published, SOTs mostly occurred simultaneously in the maxilla and mandible (n = 19/63.3%). Lesions were bifocal in 13 (43.3% of all the 30 cases) and multifocal in 17 cases (56.7% of all the 30 cases). All SOTs available in the literature presented the same type of lesion, and two of them also involved another different SOT (n = 2/6.7% of all the 30 cases). Out of all published cases, the most frequent SOTs in the literature were odontomas (n = 10/33.3% of all the 30 cases), squamous odontogenic tumors (OTs) (n = 8/26.7% of all the 30 cases), calcifying epithelial OTs (n = 8/26.7% of all the 30 cases), and adenomatoid OTs (n = 2/6.7% of all the 30 cases). Considering all SOTs cases included, the overall recurrence was 13.3%. Inside a subgroup of the lesion, synchronous calcifying epithelial OT presented the highest (25%). Five cases (16.7% of all the 30 cases) had a previously associated syndrome, with two cases of Schimmelpenning syndrome being reported. Among published SOTs, odontomas were the most common. All SOTs available in the scientific literature showed the same type of OT and mainly affected both jaws simultaneously. Only a few of these cases were associated with a syndrome.

Spatial distribution of CD34 protein in primordial odontogenic tumour, ameloblastic fibroma and the tooth germ.

BACKGROUND: Primordial odontogenic tumour is a benign mixed neoplasm of recent description, which has histological similarities with other odontogenic tumours such as the ameloblastic fibroma. In this article, we investigate the architecture of the sub-epithelial layer of mesenchymal cells expressing the marker CD34 in primordial odontogenic tumour. OBJECTIVE: Analyse the spatial patterns of CD34 expression in primordial odontogenic tumour and compare them with those in ameloblastic fibroma and the normal tooth germ by means of objective imaging approaches, to better characterise these lesions. METHODS: Two cases of primordial odontogenic tumour, four cases of ameloblastic fibroma and two cases of tooth germ in cap and bell stages were used for morphological, structural and immunohistochemical analyses. RESULTS: CD34 expression was found in vascular endothelium of primordial odontogenic tumour, ameloblastic fibroma and tooth germ. In addition, a characteristic sub-epithelial expression was observed only in primordial odontogenic tumour, corresponding to 84%-86% of the sample boundaries. Moreover, the zone expressing CD34 corresponded with a higher cellularity, which was absent in ameloblastic fibroma and tooth germ. CONCLUSION: Image analysis of the primordial odontogenic tumour architecture revealed characteristics absent in other odontogenic tumours and tooth germs. This study provides additional information to support the idea that this neoplasm is a distinct entity from early stage AF or developing odontoma.

Peripheral odontogenic keratocyst: Clinicopathological and immunohistochemical characterization.

OBJECTIVE: The aim of this study is to present and discuss the salient clinicopathological features, differential diagnosis and epithelial immunohistochemical profile of three additional cases of peripheral odontogenic keratocyst (POKC) and to present a review of the literature. POKC is a locally aggressive odontogenic lesion. The peripheral variant of the odontogenic keratocyst is rare and more frequently located in anterior gingiva. MATERIAL AND METHODS: We present the clinicopathological features of 3 new cases of POKC (2 women and 1 man; age range: 14-74 years). Immunohistochemical study included CK7, CK14, CK19 and Ki-67, and a systematic review of the literature was performed in PubMed, Scopus and Web of Science databases. RESULTS: All cases were located in the anterior gingiva (2 in maxilla and 1 mandible), and none corresponded to Gorlin-Goltz syndrome. High expression of CK14 was seen in all cases, with CK19 and CK7 been only focally positive. The expression of Ki-67 was located in the basal and parabasal cells in all cases. CONCLUSIONS: POKC is a rare gingival lesion that seems to originate from remnants of dental lamina or from the basal cells of the gingival epithelium and present a similar histopathology as compared to intraosseous OKC.

Hybrid odontogenic lesions: A systematic review of 203 cases reported in the literature.

BACKGROUND: Hybrid odontogenic lesions combine histopathological characteristics of two or more odontogenic cysts and/or tumours. The aim of this study was to evaluate the available data on hybrid odontogenic lesions (HOL) and to analyse their epidemiological/clinical features and biological behaviour. METHODS: An electronic search was done in January 2021 using multiple databases. Eligibility criteria encompassed publications with sufficient clinical and histological information to confirm the tumours' diagnoses. RESULTS: A total of 147 articles were included in this study, comprising 203 cases. Calcifying odontogenic cyst associated with odontoma (COC/OD) (37/18.2%) was the most common HOL. Females were more affected with a mean age of 24.9 years. Lesions presented as asymptomatic swellings, with a mean evolution time of 8.2 months (0.3-96), and mean tumour size of 4.8 cm (0.3-7). Radiographic aspects frequently showed radiolucent (139/68.4%) and unilocular (52/25.6%) images with well-defined limits (48/23.6%). The lesions mostly affected mandibular pre-molars (69/34%) and mandibular molars (69/34%) regions. Enucleation (89/43.8%) and surgical excision (59/29%) were the most common treatment modalities. The mean follow-up time was 33.8 months (0.5-216 months) and recurrences were observed in four cases (1.9%), all of which were central odontogenic fibroma associated with central giant cell granuloma (COF/CGCG). CONCLUSION: COC/OD is the most common HOL and recurrence is a rare event, being usually associated with the diagnosis of COF/CGCG.

Value of the toluidine blue test as an aid to determine the biopsy site in actinic prurigo cheilitis.

Actinic prurigo (AP) is a type of photodermatosis that primarily affects the Latin American mestizo population. Histologically, AP cheilitis exhibits acanthosis with spongiosis and vacuolation of the basal cell layer overlying a dense lymphocytic inflammatory infiltrate that forms well-defined lymphoid follicles. Toluidine blue is a thiazide, acidophilic, and metachromatic dye used in vivo to selectively stain the acidic components of tissues such as sulfates, carboxylates, and phosphate radicals that are incorporated into DNA and RNA. It is necessary to develop a method that allows detecting, on clinical grounds the area of the lesion in which it is more feasible to find such structures. Thus to increase the sensitivity of the biopsy, in AP cheilitis to accurately identify where the lymphoid follicles reside, based on the higher concentration of DNA in such structures and thus confirm the diagnosis. In this study, staining was positive in 85% of patients with AP cheilitis, in 14 of whom 82% lymphoid follicles were observed by histopathology. One of the pathologist's problems in establishing the diagnosis of AP is that the main histopathological characteristics are not always identified in the submitted samples because it is not easy to clinically identify the most representative site of the lesion selected for performing a biopsy. Based on our results, we propose using toluidine blue as an auxiliary method to choose a tissue sample to facilitate the diagnosis and allow clinicians to make clinical correlations between the histopathological and therapeutic findings.

Langerhans cell histiocytosis in the oral and maxillofacial region: An update.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by abnormal proliferation and infiltration of histiocytic cells. METHODS: This review focused on the main aspects associated with LCH. RESULTS: LCH can involve single or multiple organs and systems, with bone and skin being the most commonly affected sites. Regarding skeletal manifestations, the jawbones are involved in about 20%-30% of all cases. Such lesions may present as unilocular or multilocular images mainly affecting the posterior mandible. Oral soft tissue lesions may also occur, with the gingiva and hard palate being the most frequently affected sites. CONCLUSION: The diagnosis and management of LCH are challenging, requiring a multidisciplinary approach, with dentists playing a central role since oral manifestations can be the first sign of the condition.

Salivary Gland Tumors: A Retrospective Study of 164 Cases from a Single Private Practice Service in Mexico and Literature Review.

Salivary gland tumors (SGT) represent an uncommon heterogeneous group of tumors with complex clinical and pathological characteristics. The prevalence of these lesions varies between studies but has been estimated between 3 and 6% of all tumors in the head and neck region. The present study aimed to evaluate the distribution and demographic findings of salivary gland tumors diagnosed in an oral pathology service in Mexico. A retrospective descriptive cross-sectional study was performed. A total of 164 cases of SGT from a private oral pathology service were diagnosed between 2000 and 2019 in Mexico City. All cases were reviewed histologically, and demographic data and histopathological diagnoses were collected. A total of 110 (67.1%) tumors were benign, and 54 (32.9%) were malignant. The majority of patients were female (n = 100, 61.0%) with an overall female:male ratio of 1.6:1. The minor salivary glands were affected more than the major salivary glands (68.9% vs. 25.6%). The palate (n = 67, 40.9%) was the most commonly affected site, followed by the parotid gland (n = 37, 22.6%), lips (n = 16, 9.8%), and buccal mucosa (n = 14, 8.5%). Pleomorphic adenoma (n = 88; 80.0%) and mucoepidermoid carcinoma (n = 16, 29.6%) were the most frequent benign and malignant tumors, respectively. The general features of SGT from the studied Mexican population shared some similarities and differences compared to previously reported series from various parts of the world.

Primordial odontogenic tumor: report of 2 new cases.

Primordial odontogenic tumor (POT) is a recently described benign odontogenic tumor, with only 16 cases reported in the literature. We present 2 new cases of POT affecting the mandible. Case 1 is that of 12-year-old girl with an asymptomatic, slow-growing mass, causing facial asymmetry. Radiography showed a well-defined unilocular radiolucency surrounding an impacted second premolar. Case 2 is that of a 13-year-old girl with a mass involving the crown of the unerupted third molar and showing similar radiographic features. Microscopically, both lesions were composed of variably cellular fibromyxoid tissue surrounded by thin ameloblastic epithelium, with stellate reticulum-like areas, but no mineralized tissue, yielding the diagnosis of POT. Immunohistochemical analysis showed diffuse expression of CK14 in epithelial cells, whereas CK19 was expressed mainly in the basal layer. Syndecan-1 (CD138) was expressed in the stellate-like regions and in the subepithelial zone. Both patients were treated surgically, with no signs of recurrence seen after 15 and 60 months, respectively.

Central odontogenic fibroma: an international multicentric study of 62 cases.

OBJECTIVE: The aim of this study was to report the clinicopathologic features of 62 cases of central odontogenic fibroma (COdF). STUDY DESIGN: Clinical and radiographic data were collected from the records of 13 oral pathology laboratories. All cases were microscopically reviewed, considering the current World Health Organization classification of tumors and were classified according to histopathologic features. RESULTS: There were 43 females and 19 males (average age 33.9 years; range 8-63 years). Clinically, COdF lesions appeared as asymptomatic swellings, occurring similarly in the maxilla (n = 33) and the mandible (n = 29); 9 cases exhibited palatal depression. Imaging revealed well-defined, interradicular unilocular (n = 27), and multilocular (n = 12) radiolucencies, with displacement of contiguous teeth (55%) and root resorption (46.4%). Microscopically, classic features of epithelial-rich (n = 33), amyloid (n = 10), associated giant cell lesion (n = 7), ossifying (n = 6), epithelial-poor (n = 3), and granular cell (n = 3) variants were seen. Langerhans cells were highlighted by CD1a staining in 17 cases. Most patients underwent conservative surgical treatments, with 1 patient experiencing recurrence. CONCLUSIONS: To the best of our knowledge, this study represents the largest clinicopathologic study of COdF. Most cases appeared as locally aggressive lesions located in tooth-bearing areas in middle-aged women. Inactive-appearing odontogenic epithelium is usually observed within a fibrous/fibromyxoid stroma, occasionally exhibiting amyloid deposits, multinucleated giant cells, or granular cells.

An international collaborative study of 105 new cases of adenomatoid odontogenic tumors.

OBJECTIVE: The aim of this study was to report the clinicopathologic features of 105 new cases of adenomatoid odontogenic tumor (AOT) from Brazil, Guatemala, Mexico, and South Africa. STUDY DESIGN: Clinical and radiographic data were collected from records of 5 oral pathology laboratories, and all cases were microscopically reviewed. RESULTS: This series of cases included 36 (34.2%) from South Africa; 33 (31.4%) from Brazil; 23 (21.9%) from Mexico; and 13 (12.3%) from Guatemala. Seventy-two patients (68.5%) were females and 33 patients (31.4%) were males, with an average age of 19.2 years. The tumors predominantly affected the anterior maxilla (48.5%), followed by the anterior mandible (29.5%); posterior mandible (15.2%); and posterior maxilla (6.6%). Sixty-three tumors (63.6%) were follicular, 34 (34.3%) were extrafollicular, and 2 (2%) were peripheral. In most cases, the tumors caused considerable cortical expansion (average size 3.4 cm). Microscopically, most cases showed rosette-like and duct-like structures. CONCLUSIONS: This is one of the largest case series of AOTs reported in the literature and the first multicenter study involving populations from Latin America and South Africa. In a fifth of the present cases, the posterior regions of the gnathic bones were affected and the tumors demonstrated larger sizes compared with cases occurring in other populations.

Oral Amelanotic Melanomas: Clinicopathologic Features of 8 Cases and Review of the Literature.

Mucosal melanomas are aggressive tumors, rarely observed in the oral cavity. The diagnosis is based on the clinical and microscopical features. Often these tumors had variable amounts of melanin pigmentation. However, when melanin is absent, the tumors are denominated amelanotic, presenting a tendency to misdiagnosis and delayed treatment. The aim of this study was to describe the clinicopathologic features of a series of oral amelanotic melanomas (OAM). Records of all cases of OAM were retrospectively retrieved from oral pathology services from January 2002 to January 2019. Data regarding the clinical features, morphological aspects, immunohistochemical reactions, treatment, and follow-up status were collected. Eight cases of OAM were included, 6 in men and 2 in women (ratio of 3:1) ranging in age from 33 to 77 years (mean 53.6 years). Clinically, the tumors presented as masses or ulcerated swellings. The most common intraoral locations of the tumors were gingiva and palate. Cervical lymph node metastasis was detected in 3 patients at the first examination. All but one patient died from complications of the tumors after a mean follow-up period of 8.5 months. In conclusion, OAM is a very aggressive malignant tumor, and when melanin is absent, an immunohistochemical panel comprising S100, melan A, HMB45, and SOX10 should be performed.

Value of the toluidine blue test as an aid to determine the biopsy site in actinic prurigo cheilitis

Actinic prurigo (AP) is a type of photodermatosis that primarily affects the Latin American mestizo population. Histologically, AP cheilitis exhibits acanthosis with spongiosis and vacuolation of the basal cell layer overlying a dense lymphocytic inflammatory infiltrate that forms well-defined lymphoid follicles. Toluidine blue is a thiazide, acidophilic, and metachromatic dye used in vivo to selectively stain the acidic components of tissues such as sulfates, carboxylates, and phosphate radicals that are incorporated into DNA and RNA. It is necessary to develop a method that allows detecting, on clinical grounds the area of the lesion in which it is more feasible to find such structures. Thus to increase the sensitivity of the biopsy, in AP cheilitis to accurately identify where the lymphoid follicles reside, based on the higher concentration of DNA in such structures and thus confirm the diagnosis. In this study, staining was positive in 85% of patients with AP cheilitis, in 14 of whom 82% lymphoid follicles were observed by histopathology. One of the pathologist's problems in establishing the diagnosis of AP is that the main histopathological characteristics are not always identified in the submitted samples because it is not easy to clinically identify the most representative site of the lesion selected for performing a biopsy. Based on our results, we propose using toluidine blue as an auxiliary method to choose a tissue sample to facilitate the diagnosis and allow clinicians to make clinical correlations between the histopathological and therapeutic findings.

Therapeutic management of the odontogenic keratocyst. An energetic approach with a conservative perspective and review of the current therapeutic options.

BACKGROUND: Odontogenic keratocysts (OKC) are cystic lesions appearing in the jaws, usually asymptomatic with a progressive growth into the bone. Many of them are diagnosed by a routine radiological examination. MATERIAL AND METHODS: This study reports a 12-year-old girl that presented an asymptomatic large radiolucent unilocular lesion associated to the crown of 3.8 that caused displacement of the molar and the inferior alveolar canal. Differential diagnosis included OKC, unicystic ameloblastoma, ameloblastic fibroma, dentigerous cyst and orthokeratinized odontogenic cyst. Two surgical interventions were performed; first, a marsupialization, and 10 months after, the third molar extraction plus cyst enucleation, mucosa excision and the application of Carnoy's solution. RESULTS: The anatomopathological exam confirmed diagnosis of OKC. There was no evidence of recurrence after 2 years of follow-up. CONCLUSIONS: Marsupialization followed by surgical enucleation with mucosa excision and Carnoy's solution can help manage treatment of OKC, a lesion characterized by an aggressive behavior. Key words:Odontogenic keratocyst, mucosa excision, carnoy solution, third molar, tooth extraction.

KRAS mutations in brown tumor of the jaws in hyperparathyroidism.

BACKGROUND: Brown tumors are giant cell-rich lesions that result from abnormal bone metabolism in hyperparathyroidism, one of the most common endocrine disorders worldwide. Brown tumors occasionally affect the jaws and, despite well-known clinical and microscopic features, their molecular pathogenesis remains unclear. We investigated the presence of pathogenic activating mutations in TRPV4, FGFR1, and KRAS in a cohort of brown tumors since these have recently been reported in giant-cell lesions of the jaws and non-ossifying fibromas of the bones (FGFR1 and KRAS), which are histologic mimics of brown tumors. METHODS: We target sequenced 13 brown tumors of the jaws associated with primary or secondary hyperparathyroidism. As mutations in these genes are known to activate the MAPK/ERK signaling pathway, we also assessed the immunostaining of the phosphorylated form of ERK1/2 (pERK1/2) in these lesions. RESULTS: KRAS pathogenic mutations were detected in seven cases (p.G12V n = 4, p.G12D n = 1, p.G13D n = 1, p.A146T n = 1). KRAS variants of unknown significance (VUS), p.A134T and p.E37K, were also detected. All samples showed wild-type sequences for FGFR1 and TRPV4 genes. The activation of the MAPK/ERK signaling pathway was demonstrated by pERK1/2 immunohistochemical positivity of the brown tumors´ mononuclear cells. CONCLUSION: Mutations in KRAS and activation of the MAPK/ERK signaling pathway were detected in brown tumors of hyperparathyroidism of the jaws, expanding the spectrum of giant cell lesions whose molecular pathogenesis involve RAS signaling.

Odontogenic Carcinoma With Dentinoid in Long-Term Follow-up With 2 Recurrences.

Dentinoid has been mentioned as a frequent component in several types of benign odontogenic tumors; however, there are some other very rare dentinoid-producing odontogenic tumors that have been described, which are not recognized in the current World Health Organization Histological Classification of Odontogenic Tumours. In this context, we report an unusual malignant odontogenic tumor containing dentinoid located in the left maxilla of a 41-year-old man. The lesion was initially diagnosed and treated as a cemento-ossifying fibroma. After 7 years, a tumor was noted at the same location and was diagnosed as pleomorphic adenoma. The patient developed a new lesion 2 years later. Histological features included an epithelial proliferation of basaloid and clear cells, some with peripheral palisading, which were scattered both in a fibrous stroma and within an amorphous eosinophilic dentinoid product. Because of doubts about the first 2 diagnoses and the current situation, all histopathological slides were reviewed in our service as a consultation case, and the findings were consistent with the diagnosis of an odontogenic carcinoma with dentinoid. Immunohistochemical analysis was performed and an ultrastructural study by scanning electronic microscopy and energy-dispersive X-ray microanalysis was made to characterize dentinoid material. After 1 year of follow-up, the patient is alive and free of the disease. This case highlights the wide variability regarding cytological evidence of malignancy, and adds a new case of odontogenic carcinoma with dentinoid, which represents a distinct entity with locally aggressive behavior and should be considered be included in a future World Health Organization Histological Classification of Tumours.