Histopathological findings and immunohistochemical expression of the stem cell markers CD44, ALDH1, Bmi-1, and Nanog in oral solitary fibrous tumors.

OBJECTIVES: The aim of this study was to evaluate the histomorphologic presentation and the expression of stem cell-related markers in a series of oral solitary fibrous tumors (SFTs). STUDY DESIGN: Histopathological variables and the expression of the standard stem cell markers CD34 and CD99, used for SFT diagnosis, as well as STAT6 were evaluated in 13 oral SFTs. The expression of the cancer stem cell markers CD44, ALDH1, Bmi-1, and Nanog and the tumor suppressor gene p16Ink4a were also investigated. RESULTS: The majority of oral SFTs were circumscribed and characterized by a proliferation of spindle cells arranged in a hyalinized stroma. Only 2 oral SFTs showed >4 mitoses/10 high-power fields. Hypercellularity as well as nuclear and cellular pleomorphism were classified as low and moderate in most of the oral SFTs. All oral SFTs were positive for CD34, STAT6, CD44, ALDH1, Bmi-1, and p16Ink4a. CD99 and Nanog expression was observed in 11 and 10 oral SFT cases, respectively. CONCLUSION: We suggest that STAT6 and ALDH1 have relevant diagnostic value. The expression of CD44, ALDH1, Bmi-1, and Nanog, which is observed in cancer stem cells, may confer advantages to oral SFT cells.

A multicenter study of oral sarcomas in Brazil.

OBJECTIVES: The aim of this study was to investigate the prevalence of oral sarcomas from geographic regions of Brazil. MATERIALS AND METHODS: A cross-sectional study was conducted on biopsies obtained from January 2007 to December 2016 at twelve Brazilian oral and maxillofacial pathology centres. Gender, age, evolution time, clinical aspects, tumour location, tumour size at diagnosis, radiographic aspects and histopathological diagnosis were evaluated. Data were analysed using descriptive statistical methods. RESULTS: From 176,537, a total of 200 (0.11%) oral sarcomas were reported, and the most prevalent were osteosarcomas (74 cases; 37%) and Kaposi's sarcomas (52 cases; 26%). Males were more affected than females at a mean age of 32.2 years old (range of 3-87 years). The most common symptoms were swelling¸ localised pain and bleeding at a mean evolution time of 5.14 months (range <1-156 months). The lesions were mostly observed in the mandible (90 cases; 45%), with a mean tumour size of 3.4 cm (range of 0.3-15 cm). Radiographically, the lesions presented a radiolucent aspect showing cortical bone destruction and ill-defined limits. CONCLUSIONS: Oral sarcomas are rare lesions with more than 50 described subtypes. Osteosarcomas and Kaposi's sarcomas were the main sarcomas of the oral cavity in Brazil.

Metastatic Renal Cell Carcinoma to the Oral Cavity.

Metastases to the oral cavity are extremely rare events, representing less than 1% of all malignant oral tumors. Renal cell carcinoma constitutes about 3% of solid tumors in adults, and it is the most frequent kidney neoplasm, representing about 90% of kidney malignancies. Due to the silent growth of this neoplasm, most patients have no symptoms and the diagnosis is belated, usually after metastases. The present study reports an additional patient of metastatic renal cell carcinoma to the oral cavity regarding the clinical and pathologic features.

Macrophage migration inhibitory factor induces phosphorylation of Mdm2 mediated by phosphatidylinositol 3-kinase/Akt kinase: Role of this pathway in decidual cell survival.

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway has an anti-apoptotic effect through several downstream targets, which includes activation of the transformed mouse 3T3 cell double-minute 2 (Mdm2) protein, its translocation to the nucleus and degradation of the tumor suppressor p53. We show that Mif, the Macrophage Migration Inhibitory Factor, an important cytokine at the maternal fetal interface in several species, triggers phosphorylation of Mdm2 protein in a PI3K/Akt-dependent manner, thereby preventing apoptosis in cultured mouse decidual cells. Inhibition of Akt and PI3K suppresses the pathway. Mif treatment also changes the nuclear translocation of p53 and interferes with the apoptotic fate of these cells when challenged with reactive oxygen species. In conclusion, an important mechanism has been found underlying decidual cell survival through Akt signaling pathway activated by Mif, suggesting a role for this cytokine in decidual homeostasis and in the integrity of the maternal-fetal barrier that is essential for successful gestation.

In Situ Melanoma of the Gingiva Associated with Dense Inflammation and Pigment Deposition: A Potential Diagnostic Pitfall in Evaluating Stromal Invasion.

Melanoma is a highly aggressive neoplasm in which the neoplastic cells display melanocytic differentiation. Less than 1 % of all melanomas arise in the mucosal surfaces of the oral cavity, with purely in situ lesions being exceedingly rare tumors, but with a favorable prognosis compared with invasive lesions. We describe the clinical, histopathological and immunohistochemical findings in an uncommon case of in situ mucosal melanoma of the oral cavity with intense tumor-associated pigment deposition and inflammation complicating the morphological assessment of infiltrative areas.

Evaluation of fine needle aspiration biopsy in oral cavity and head and neck region with different stains techniques.

The present study aimed to evaluate the Fine Needle Aspiration Biopsy in different staining techniques in nodular lesions of the oral cavity and head and neck region, as their sensitivity, specificity and accuracy, staining with Panoptic, Papanicolaou and Hematoxylin-Eosin (H&E) stains. 46 patients who sought the Clinic of the Discipline of Clinical Stomatology at FOUSP were selected consecutively, with nodular lesions in the oral cavity and head and neck region. The material obtained by FNAB was sent on 6 different slides, stained by the method of Panoptic, Papanicolaou and H&E, to the same pathologist only with the clinical diagnosis. After the final report of FNAB, the biopsy report was issued, serving as gold standard. After the calculations, the results of sensitivity, specificity and accuracy for Panoptic staining were 28.6%, 76% and 15.4%, respectively. The result of sensitivity, specificity and accuracy for Papanicolaou staining were 71.4%, 76.7% and 23.3%, respectively. The result of sensitivity, specificity and accuracy for H&E staining were 82.1%, 23.3%, 28.6%, respectively. We can conclude, according to the methodology of this study that, H&E and Papanicolaou stains showed the same sensitivity of diagnosing malignant neoplasms. H&E stain showed a better specificity for diagnosing benign neoplasms, compared with Papanicolaou and Panoptic stains. H&E stain showed better accuracy, to give definitive diagnosis, followed by Papanicolaou and Panoptic stains.

Histologic, histomorphometric, and radiographic monitoring of bone healing around in-office-sterilized orthodontic mini-implants with or without immediate load: study in rabbit tibiae.

PURPOSE: The objective of this study was to describe bone healing around self-drilling orthodontic mini-implants (MIs), sterilized in an office with an autoclave, with or without immediate orthodontic loading. MATERIALS AND METHODS: One hundred forty-four self-drilling MIs (TOMAS, Dentaurum) were inserted into the tibiae of 18 white rabbits, with full-thickness flaps elevated under general anesthesia. An immediate load (50 cN) was applied to 50% of the MIs. Two rabbits were sacrificed soon after the surgery and served as a control group. Four rabbits each were sacrificed at 15, 21, 30, or 60 days after the surgeries. Digital radiographs were obtained to measure the cortical bone thickness (CBT) around and between the implants. Sections were obtained and stained for histologic and histomorphometric analysis. Bone quantity (BQ), bone-to-implant contact (BIC), and CBT were evaluated statistically. RESULTS: At day 0, fractures were visible in the cortical area around the MIs. At days 15 and 21, intense proliferation of woven bone followed by formation of lamellar bone was seen. After 30 days, primary bone was visible, with less proliferation activity. At day 60, primary bone in the process of remodeling into secondary bone was apparent. BQ was better with loading after 15 days and increased throughout the healing period in the loaded and unloaded groups. Loading did not influence the BIC values, which increased with healing time for loaded and unloaded implants. CBT increased in all regions, and CBT was greater around the MIs than between them except for unloaded MIs in the 15-day group. CONCLUSION: An immediate, light orthodontic load did not affect the bone healing process around orthodontic MIs. Osseointegration and CBT increased and were time-related.

MCM3 could be a better marker than Ki-67 for evaluation of dysplastic oral lesions: an immunohistochemical study.

BACKGROUND: The aim of this study was to identify the expression of MCM3, Ki-67 and p27 in normal mucosa, leucoplakia and oral squamous cell carcinoma (OSCC) and determine whether altered expression could serve as a prognostic marker of a malignant progression of dysplastic lesions. METHODS: The samples were collected from 37 patients with oral leucoplakia (13 with mild dysplasia - MLD, 12 with moderate dysplasia - MD and 12 with severe dysplasia - SD). Eleven samples of mouth floor mucocele (M) and 50 floor mouth and tongue samples OSCC of untreated patients were included in this study. Immunohistochemical expression of MCM3, Ki-67 and p27 of all the groups was analysed. Kruskal-Wallis and Dunn's test were used to determine differences among groups, and a Pearson's correlation test was used to evaluate the correlation between the proteins. RESULTS: Ki-67 expression was higher in OSCC than M (P < 0.001) and MLD (P < 0.01) groups, and there was a lower expression in M compared with MD and SD (P < 0.05). Regarding p27, its expression was lower in OSCC compared with M, MD and SD. MCM3 expression was lower in M compared with SD and OSCC (P < 0.001), and MLD showed a lower expression when compared SD (P < 0.01) and OSCC (P < 0.001). Moreover, a better correlation was observed between the proteins MCM3 and p27 than between Ki-67 and p27 proteins when all lesions were examined together. CONCLUSIONS: This study showed that MCM3 could be a better marker than Ki-67 for evaluation of dysplastic oral lesions.

Effectiveness of surgical decompression in the treatment of a calcifying cystic odontogenic tumor.

The calcifying odontogenic cystic tumor (CCOT) is a benign lesion of odontogenic origin characterized by an ameloblastoma-like epithelium with ghost cells that may calcify. Despite broadly considered as a cyst, some investigators prefer to classify it as a neoplasm. Clinically, it occurs predominantly during the third decade of life. No difference in gender prevalence has been observed nor predilection of the lesion between maxilla and mandible. The most affected region extends from the incisor tooth to bicuspids. The classic treatment of the lesion is full excision, although a different approach may be determined by the possible association with another odontogenic tumor. Depending on the tumor size and the vicinity with important structures, decompression may be undertaken before its complete removal. The present report describes a case of CCOT with large proportions, located at the right maxilla and extending to the maxillary sinus, nasal cavity, and orbital floor. The treatment option was surgical decompression as the initial procedure, with satisfactory outcome. After partial remission, the lesion was fully removed, and the post-operative follow-up was uneventful.

Clinical and histological features of multifocal canalicular adenomas of the upper lip.

Canalicular adenoma (CA) is an uncommon benign salivary gland tumor that mostly occurs in the upper lip. Despite its benign nature, some patients may present multiple nodules and also microscopic growth that can be multifocal with foci of tumor within the adjacent gland. Microscopically, CA can be mistaken for a polymorphous low-grade adenocarcinoma (PLGA) or basal cell adenoma (BCA), and immunohistochemistry can be helpful in differentiating them. Two cases of canalicular adenoma showing tumor foci within the adjacent gland are described. Both cases occurred in the upper lip of white females aged 72 and 79 years. In addition to the histological multifocal aspect, one of the patients presented bi-lateral nodules. Histological examination of both lesions revealed interconnecting and branching canal-like structures composed by uniform columnar and sometimes cuboidal cells, partially encapsulated. Immunohistochemical analysis showed intense expression of cytokeratins (CK) 7, a weak reaction to CK14 and a negative reaction to vimentin. Upon the diagnosis of CA the lesions were excised. In conclusion, it is important to properly diagnose CA and differentiate its multifocal aspect from a malignant behavior.

Oral leukoplakia manifests differently in smokers and non-smokers.

Oral leukoplakias (OL) are potentially malignant lesions that are typically white in color. Smoking is considered a risk factor for developing OL, and dysplastic lesions are more prone to malignant transformation. The aim of this study was to describe the clinical features observed in dysplastic and non-dysplastic OL in both smokers and non-smokers. A total of 315 cases of OL were retrieved and separated into either dysplastic or non-dysplastic lesions, and these cases were further categorized as originating in either smokers or non-smokers. Frequencies of the type of OL lesion, with respect to whether the patients smoked, were established. The results demonstrated that 131 cases of OL were dysplastic (74 smokers and 57 non-smokers), and 184 were non-dysplastic (96 smokers and 88 non-smokers). For OL cases in smokers for which information about alcohol consumption was also available (84 cases), the results revealed no significant difference in the amount of dysplastic and non-dysplastic lesions. Dysplastic lesions were more frequent in male smokers and in non-smoking females. The median age of smokers with cases of OL was significantly lower than in non-smokers; the lowest median ages were observed for female smokers with dysplastic OL. The most frequent anatomical sites of dysplastic lesions were the floor of the mouth in smokers and the tongue in non-smokers. Dysplastic lesions in smokers were significantly smaller than non-dysplastic lesions in non-smokers. Being a male smoker, being female, being younger, and having smaller lesions were associated with dysplastic features in OL. These clinical data may be important for predicting OL malignant transformation.

Central granular cell odontogenic tumor of the maxilla.

The central granular cell odontogenic tumor (CGCOT) is a rare benign odontogenic neoplasm composed of varying amounts of large eosinophilic granular cells and apparently inactive odontogenic epithelium. It tends to occur as a small asymptomatic swelling in the posterior region of the mandible with nonaggressive appearance. We report an unusual case of CGCOT in the maxillary region with clinical features of malignancy. The patient underwent surgical treatment, and the 2-year follow-up revealed no signs of recurrence. Central granular cell odontogenic tumor is a very rare condition with few cases reported, especially in the maxillary region. This case highlights the possibility of aggressive behavior by these lesions.

Report of four cases of ameloblastic fibro-odontoma in mandible and discussion of the literature about the treatment.

The ameloblastic fibro-odontoma is defined as a tumour with the general features of the ameloblastic fibroma but that also contains enamel and dentine. AFO normally presents as a painless swelling in the posterior portion of the maxilla or mandible. Radiographs show a well-defined radiolucent area containing various amounts of radiopaque material of irregular size and form. The most appropriate treatment for a large AFO has not been completely determined. This paper reports four large AFO cases and reviews the relevant literature regarding the clinical and surgical features of this lesion.

Squamous cell carcinoma of the tongue and floor of the mouth: analysis of survival rate and independent prognostic factors in the Amazon region.

Oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity. Although several studies have shown the epidemiology of this cancer in Brazil, there do not seem to be any studies that describe the prognostic factors related to OSCC in the Amazon region. Therefore, the aim of this study was to determine the survival rate and prognostic significance of different factors in patients from this region affected by OSCC. Data from 85 patients with histologically confirmed squamous cell carcinoma of the tongue and floor of the mouth identified from the Ofir Loyola Hospital archives were collected and analyzed using univariate (log-rank test) and multivariate (Cox proportional hazard model) tests. The overall 5-year survival rate was found to be 27%. Univariate analysis showed that the 5-year survival rate was significantly higher for younger (≤ 45 y) female patients, patients with T1-2 tumors and clinically clear neck nodes (N0), patients with early stage cancers (AJCC stage I-II), and patients treated with surgical procedures. However, multivariate analysis showed that the 5-year survival rate was significantly higher only in the younger patients and those who underwent surgical treatment. The age of the patient at the moment of diagnosis and treatment with surgical procedures were the only independent prognostic factors that affected the 5-year survival rate of the patients in this region.

Altered ß-catenin expression related to cancer progression on actinic cheilitis and squamous cell carcinoma of the lip.

ß-Catenin is a bifunctional protein related to cell adhesion and gene transcription when activated by Wnt pathway. Altered expression of ß-catenin was related to loss of differentiation, more aggressive phenotype, increase of tumor invasion, and poor prognosis in a number of different cancers. Actinic cheilitis is caused by excessive exposure to ultraviolet radiation and has a high potential to suffer malignant transformation into squamous cell carcinoma (SCC) of the lip, the most frequent oral malignancy. Studies of oral cancer have shown the correlation of ß-catenin expression and oral SCC prognosis, and loss of membrane expression may be considered as a potential marker for early tumor recurrence. Thirty-five cases of actinic cheilitis and 12 cases of SCC of the lip were select and submitted to immunohistochemical staining using ß-catenin antibody. ß-Catenin was positive on the membrane for all cases. Eighty-five percent of actinic cheilitis cases showed cytoplasmatic staining, and 22% nuclear staining. Eighty-three percent of SCC was positive for ß-catenin, and none of them had nuclear staining. Cytoplasmatic and nuclear staining of ß-catenin on studied cases point to pathway alterations. Results demonstrated that ß-catenin expression is altered on epithelial dysplasia, and it is related to degree of alterations.

The neural histogenetic origin of the oral granular cell tumor: an immunohistochemical evidence.

AIMS: Granular cell tumor (GCT) is a rare neoplasm that can appear in any site of the body, but most are located intraorally. Its histogenetic origin remains unclear. This report analyzes the immunoprofile of 15 cases of granular cell tumors, occurring in 13 women and 2 men and the lesions were located on the tongue or upper lip. Patient age ranged from 7 to 52. METHODS: The patients demographic data and the cytological and architectural features of the lesions were analyzed in oral GCTs (n=15). The lesions were also submitted to a panel of immunohistochemical stains with antibodies against S-100, p75, NSE, CD-68, Ki-67, Synaptofisin, HHF-35, SMA, EMA, Chromogranin, Progesterone, Androgen and Estrogen. RESULTS: Among the fifteen cases analyzed, the most common location was the tongue (84.6%). Histologically, the tumors exhibited cellular proliferation composed mainly by polygonal cells presenting an abundant granular eosinophilic cytoplasm. The nuclei were central, and the cell membranes were moderately clear. No mitotic figures were observed. The immunohistochemical analysis showed positivity in all cases for S-100, p75, NSE and CD-68, and no immunoreactivity for Ki-67, Synaptofisin, HHF-35, SMA, EMA, Chromogranin, Progesterone, Androgen and Estrogen. CONCLUSION: The immunoprofile of granular cell tumors showed nerve sheath differentiation--lending support to their neural origin--and helping to establish a differential diagnosis between this lesion and other oral granular cell tumors, whether benign or malignant.

Angiomyolipomatous hamartoma of the upper lip: a rare case in an 8-month-old child and differential diagnosis.

Hamartoma is a proliferation of normal tissues that are considered endogenous to the site of occurrence. In the head and neck region, hamartomas composed of other tissues different from blood and lymphatic vessels (hemangiomas and lymphangiomas) are very uncommon. We report an unusual case of upper lip angiomyolipomatous hamartoma in an 8-month-old patient. The patient underwent surgical treatment and the 1-year follow-up revealed no signs of recurrence. Angiomyolipomatous hamartoma is a very rare condition in the paediatric population group, especially in the head and neck region. It should be considered in the differential diagnosis of congenital lesions in childhood.

Solitary neurofibroma of the temporal bone.

Neurofibroma is a benign peripheral nerve sheath tumor that can be occasionally found in the head and neck region as multiple lesions associated with neurofibromatosis type 1 (NF-1) or as a solitary tumor. The real frequency of isolated neurofibromas not associated with NF is uncertain, and lesions in the temporal region are extremely rare. The aim of the current article was to report an unusual case of solitary neurofibroma localized in the temporal and infratemporal regions with 10 years of evolution in a female patient without any other manifestation or familiar history of NF-1. The patient underwent surgical treatment for complete excision of the lesion, and the 2-year follow-up revealed no signs of recurrence.

Oral manifestations of vitamin B12 deficiency: a case report.

Megaloblastic anemias are a subgroup of macrocytic anemias, in which distinctive morphologic abnormalities occur in red cell precursors in bone marrow, namely megaloblastic erythropoiesis. Of the many causes of megaloblastic anemia, the most common are disorders resulting from cobalamin or folate deficiency. The clinical symptoms are weakness, fatigue, shortness of breath and neurologic abnormalities. The presence of oral signs and symptoms, including glossitis, angular cheilitis, recurrent oral ulcer, oral candidiasis, diffuse erythematous mucositis and pale oral mucosa offer the dentist an opportunity to participate in the diagnosis of this condition. Early diagnosis is important to prevent neurologic signs, which could be irreversible. The aim of this paper is to describe the oral changes in a patient with megaloblastic anemia caused by a dietary deficiency of cobalamin.

MDM2, P53, P21WAF1 and pAKT protein levels in genesis and behaviour of adenoid cystic carcinoma.

BACKGROUND: MDM2, P53, P21(WAF1) and pAKT are proteins associated with the balance between cell death and survival. There are many hypotheses regarding the role of these proteins in salivary gland tumours. However, many molecular events that activate or inactivate regulatory genes remain unknown. The aim of this study was to evaluate and to correlate MDM2, P53, P21(WAF1) and pAKT protein expressions in adenoid cystic carcinomas (ACC). METHODS: Twenty-two cases of ACC were evaluated by immunohistochemistry and one cell line derived from ACC was analyzed by Western Blotting and immunofluorescence techniques. RESULTS: Strong MDM2 and pAKT, variable P53 and null P21 expressions were found in the cases analyzed, but no statistical correlation was established when comparing MDM2 and pAKT expressions in the 3 different ACC subtypes. The ACC cell line showed intense nuclear and cytoplasmatic MDM2 and pAKT expressions and null P53 and P21 expressions. CONCLUSIONS: Results indicate that MDM2 and pAKT are related to the tumorigenesis of ACC, but they might not be directly connected to tumour progression. We also demonstrate that the pAKT pathway is active in ACC and it seems to be activating the MDM2 shuttle from the cytoplasm to the nucleus, where it phosphorylates P53 and carries it to the cytoplasm for degradation.