E-cadherin downregulation and Twist overexpression since early stages of oral carcinogenesis.

There is some evidence of Twist participation in oral carcinogenesis; however, little is known about its interaction with E-cadherin in oral squamous cell carcinoma (OSCC) development. This experimental study included an immunohistochemical analysis of Twist and E-cadherin proteins in paraffin-embedded specimens of oral leukoplakia (OL), OSCC, and normal oral mucosa. In addition, it was also performed a Western blot and double-immunofluorescence analysis of Twist and E-cadherin expression in OSCC cell lines. Significant differences in Twist and E-cadherin immunoexpression were observed between normal oral mucosa and OL, with an inverse relation since the earliest stages of oral dysplasia (r = -0,512; P < 0.001). Western blot and double-immunofluorescence analysis showed differences in Twist and E-cadherin expression among human oral keratinocytes and OSCC cell lines suggesting that downregulation of E-cadherin occurs in a dependent manner of Twist in OSCC. Our results showed a possible value of Twist and E-cadherin in the prediction of risk of oral epithelium malignant transformation.

Burkitt's lymphoma of the jaws in the Amazon region of Brazil.

OBJECTIVE: To describe the clinicopathologic and immunohistochemical features of Burkitt's lymphoma of the jaws in 7 patients of Northern Brazil. STUDY DESIGN: Clinical data concerning gender, age, affected site, clinical presentation, symptomatology and follow-up were collected from the clinical files. Histopathology was complemented with a broad immunohistochemical panel and in situ hybridization for Epstein-Barr virus (EBV). RESULTS: Most of the patients were infants and 5 out of 7 were males. The mandible was affected in 5 cases and all patients also presented abdominal involvement. All cases were positive for CD45, CD20, CD79a, CD10, Bcl-6 and EBV. Ki-67 proliferative index was approximately 100%. Six patients were treated with R-CHOP (Rituximab + Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone) chemotherapy, and 2 of these died of the disease. One young adult patient refused treatment and died 3 months after initial diagnosis. CONCLUSION: Burkitt's lymphoma of the jaws diagnosed in the Amazon region of Brazil present similar clinicopathologic features to those described in endemic areas of Africa, including EBV positivity.

Effects of celecoxib treatment over the AKT pathway in head and neck squamous cell carcinoma.

BACKGROUND: Celecoxib, a non-steroidal anti-inflammatory drug that selectively inhibits cyclooxygenase-2 (COX-2), has shown an important anticarcinogenic effect for the treatment of squamous cell carcinoma. The use of COX-2 inhibitors has effectively inhibited the growth of Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines, while a recent phase 1 trial demonstrated good response rate of cancer cells to this drug with minimal toxicity. Possible targets of celecoxib include proteins involved in cell proliferation and apoptosis control. Additionally, celecoxib antitumoral activity has been linked with a COX-2-independent event. METHODS: To better understand which cellular mechanisms are targeted by celecoxib, its effects upon the Akt signaling pathway using two different HNSCC cell lines were analyzed through cell viability assay, immunofluorescence, and Western blotting. RESULTS: The results showed decreased levels of Cyclin D1 and pAkt protein expression in vitro. The number of viable cells was also diminished after celecoxib treatment. CONCLUSION: As Akt pathway seems to be a valuable target for the HNSCC therapy, the results presented herein confirm that celecoxib can be considered as an alternative adjuvant drug for HNSCC treatment.

Oestrogens and androgen receptors in oral squamous cell carcinoma.

OBJECTIVE: To investigate the gender-related expressions of androgen (AR), estrogen alpha (ERα) and beta (ERß) receptors and aromatase enzyme in oral squamous cell carcinomas (OSCC). MATERIALS AND METHODS: A total of 60 cases of OSCC (30 from males and 30 from females) were retrieved and submitted to immunohistochemistry. Also, steroid expression was studied in two OSCC cell lines using Western blotting and immunofluorescence. RESULTS: Immunohistochemistry demonstrated that ERß was expressed in almost 40% of the cases and AR in 26%. Aromatase enzyme and ERα were less commonly expressed. Only AR presented statistically significant differences between genders. Western blotting and immunofluorescence analysis demonstrated that ERß was abundantly expressed in the nuclei of both cell lines and aromatase enzyme presented a cytoplasmic expression. CONCLUSION: The detection of steroid hormones, especially ERß, can indicate a role of these proteins in the process of carcinogenesis of some OSCC. Further studies of the mechanisms involved may provide important biological information regarding therapeutic approaches.

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil.

This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

TWIST and p-Akt immunoexpression in normal oral epithelium, oral dysplasia and in oral squamous cell carcinoma.

OBJECTIVES: The aim of this study was to evaluate the immunoexpression of TWIST and p-Akt proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC), correlating their expressions with the histological features of the lesions. STUDY DESIGN: Immunohistochemical studies were carried out on 10 normal oral epithelium, 30 OL and 20 OSCC formalin-fixed, paraffin-embedded tissue samples. Immunoperoxidase reactions for TWIST and p-Akt proteins were applied on the specimens and the positivity of the reactions was calculated for 1000 epithelial cells. RESULTS: Kruskal-Wallis and Dunn's post tests revealed a significant difference in TWIST and p- Akt immunoexpression among normal oral mucosa, OL and OSCC. In addition, a significant positive correlation was found between TWIST and p-Akt expressions according to the Pearson's correlation test. CONCLUSIONS: The results obtained in the current study suggest that TWIST and p-Akt may participate of the multi-step process of oral carcinogenesis since its early stages.

Different expression patterns of pAkt, NF-κB and cyclin D1 proteins during the invasion process of head and neck squamous cell carcinoma: an in vitro approach.

BACKGROUND: Several signaling pathways are involved in the progression of squamous cell carcinoma. Among them, activated PI3K/Akt may result in NF-κB nuclear translocation, thus leading to the transcription of genes enrolled in cellular invasion and proliferation, such as cyclin D1. This study sought to evaluate the expression of pAkt, NF-κB and cyclin D1 proteins in head and neck squamous cell carcinoma cell lines and their respective in vitro-obtained invasive clones. METHODS: Squamous cell carcinoma cell lines originating from the tongue, pharynx and the metastatic lymph node were submitted to an in vitro invasion assay to select invasive clones. All experimental groups were submitted to immunofluorescence and Western blot assays. Statistical analysis was performed through a Student's t-test with a significance level of 5%. RESULTS: The pAkt and NF-κB expression differed from cytoplasm and nucleus depending on the studied cell line. The invasive clone from the tongue presented a network-like structure of pAkt's cytoplasmic expression. This lineage as well as the invasive clone from pharynx also showed pAkt and NF-κB nuclear transportation. Significant pAkt and NF-κB increases were observed in the tongue and pharynx invasive clones. Cyclin D1 was detected in the nucleus of all studied cells and was significantly enhanced in the invasive clones from tongue and pharynx. CONCLUSION: This study suggests the participation of pAkt, NF-κB and cyclin D1 in the invasion process of head and neck squamous cell carcinoma. Moreover, cytoplasmic pAkt network-like structure was probably related to cytoskeleton changes presented during invasion.

Immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in a case of ameloblastic fibrosarcoma.

Ameloblastic fibrosarcoma (AFS), regarded as the malignant counterpart of the benign ameloblastic fibroma, is an extremely rare odontogenic neoplasm with only 68 cases reported in the English literature up to 2009. It is composed of a benign odontogenic epithelium, resembling that of ameloblastoma, and a malignant mesenchymal part exhibiting features of fibrosarcoma. Due to the rarity of the lesion, little is known about its molecular pathogenesis; therefore, in the current study, we sought to evaluate the immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in AFS, comparing the results obtained with its benign counterpart, as well as to report a new case of this rare entity affecting a 19-year-old female patient. The results obtained revealed that all the proteins evaluated were overexpressed in the malignant mesenchymal portion of AFS if compared with ameloblastic fibroma, suggesting that nuclear proliferative factors such as Ki67 and proliferative cell nuclear antigen, in association to histopathologic features, may be useful markers for identifying the malignancy and that, despite the lack of molecular analysis in the case reported, Bcl-2 alteration may play a role in AFS pathogenesis.

Granulocytic sarcoma of the oral cavity in a chronic myeloid leukemia patient: an unusual presentation.

Intraoral granulocytic sarcoma is an unusual manifestation of chronic or acute leukemia. The oral manifestations often involve enlargements of the gingival and mucosal tissue from direct leukemic cell infiltration. Only 38 cases have been reported in scientific literature to date. We present the case of a 47 year-old female who was diagnosed with chronic myeloid leukemia (CML) in December 2006. She was referred to a dentist for further evaluation, revealing generalized gingival overgrowth as well as periodontal, apical disease, and bleeding of the gums. An oral biopsy was performed and histological features revealed immature blast-like cells.

Mesenchymal Stem Cell Marker Expression in Periapical Abscess.

INTRODUCTION: There is evidence that acute periapical lesions present a greater potential for cyst formation. Recently, it was found that these lesions have cells with characteristics of pluripotent stem cells, which may influence cyst development. However, a more complete phenotype investigation of stem cells in a specific sample of periapical abscesses is required. The aim of this study was to analyze the immunohistochemical expression of mesenchymal stem cell (MSC) markers in periapical abscesses and to evaluate differences in their expression in relation to acute and chronic periapical lesions. METHODS: Immunohistochemistry was used to access MSC marker expression (CD44, CD73, and CD105) in samples of periapical abscesses (n = 10), granulomas (n = 10), cysts (n = 10), and apical papillae (n = 10). Immunohistochemical expression was evaluated by a quantitative scoring system. The chi-square test was used to assess the association between MSC marker expression and the histopathological diagnosis at a 5% significance level. RESULTS: CD44 and CD73 immunostaining was observed in mesenchymal cells located in the outer portion of the abscess and periapical cyst specimens. CD105 immunoexpression was found predominantly in mesenchymal and vascular endothelial cells of the lesions studied. MSC marker expression was higher in the periapical abscesses, with a significant association between MSCs and the histopathological diagnosis of an abscess (P < .05). CONCLUSIONS: The periapical region is a rich source of MSCs. The greater presence of MSCs in periapical abscesses found in this study could hold an important clue into understanding the pathological pathway of periapical cyst formation.

Nuclear metallothionein in oral squamous cell carcinoma: clinicopathological parameters and patient survival.

The aim of this study was to identify the immunoexpression of methallothionein in oral squamous cell carcinoma as well as to address the correlation with clinical features, histological grade and patient survival. Samples were collected from 93 patients with tongue squamous cell carcinoma who presented for follow-up. Immunohistochemical expression of methallothionein in all groups was performed. The scoring system has previously been published by Tsurutani in 2005, which is based on intensity and distribution of staining. We used Kappa index to evaluate the degree of observers' agreement under metallothionein immunostaining and histological grade. Associations between methallothionein expression and clinical parameters (age, gender, smoking, tumor size, lymph node metastasis and disease stage) were examined for statistical significance using the chi-squared test. The overall survival rates were estimated by the Kaplan-Meier method and the relationship between protein expression and survival was compared using the log-rank test (p < 0.05). Our results showed no statistically significant association between methallothionein immunostaining and the selected clinicopathological variables. Immunohistochemistry results showed positive nuclear immunostaining for metallothionein in 62,37% (58/93) and negative for metallothionein 37,63% (35/93). The degree of examiners agreement by Kappa varied from substantial to perfect and both metallothionein immunostaining and histological grade were explored. The present study suggests that positive methallothionein expression found in tongue squamous cell carcinoma may not help to predict survival in the analyzed samples, as well as no relation between the protein and histological grade and clinical features was observed. In conclusion, the present study suggests that metallothionein is not associated with tongue squamous cell carcinoma clinicopathological characteristics and aggressiveness.

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil

Abstract This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

Chondroblastic osteosarcoma mimicking periapical abscess.

CASE REPORT: The present report describes a case of chondroblastic osteosarcoma in the periapical region of teeth #29, #30, and #31 of an 18-year-old male. Clinical history showed self-reported discomfort in the right posterior gingiva for over a month. Physical examination showed a small expansion and redness of the right mandibular buccal and lingual cortical plates, but no signs of pain or inflammation were observed. All the teeth responded positively to pulp sensibility. Periapical and panoramic radiographs showed slight periapical radiolucency in the roots of teeth #29 and #30, clear periodontal ligament space widening, and evident loss of lamina dura. Incisional biopsy was performed, and based on microscopic findings the diagnosis of chondroblastic osteosarcoma was confirmed. CONCLUSIONS: Non-endodontic diseases associated with tooth root apex, such as chondroblastic osteosarcoma, should be included in differential diagnosis of jaw lesions that resemble periapical abscess.

Stem Cell Marker Expression in Persistent Apical Periodontitis.

INTRODUCTION: This study evaluated the expression of CD90 (mesenchymal stem cell) and Sox2 (progenitor stem cell) markers in persistent apical periodontitis (PAP) (n = 16) and primary periapical lesions (PPLs) (n = 10). METHODS: All samples were classified histologically according to the intensity of inflammatory cell infiltrate in the periapical lesion. Immunohistochemistry was used to detect CD90 and Sox2 in PAP and PPLs. The Spearman correlation coefficient and the Mann-Whitney U test were used to analyze data at the 5% significance level. RESULTS: CD90 expression was found in mesenchymal cells and vascular endothelial cells of 68.5% of all cases of PAP. There was no correlation between CD90 expression and histopathological diagnosis (P = .053) or inflammatory cell infiltrate intensity (P = .112). CD90 staining was predominantly found in the vascular endothelial cells of 30% (n = 3) of PPLs. CD90 expression was significantly higher in PAP than in PPLs (Mann-Whitney U test, P < .05). Sox2 expression was found in all cases of PAP. Eventually, all mesenchymal and chronic inflammatory cells exhibited Sox2 expression. There was no correlation between Sox2 expression and histopathological diagnoses (P = .749), inflammatory cell infiltrate intensity (P = .510), or acute or chronic inflammatory cell infiltrate (P = .256). Sox2 expression was found in 100% of PPLs. There was no difference in Sox2 expression between PAP and PPLs (P = .477). CONCLUSIONS: Mesenchymal stem cells may contribute to the immunosuppressive environment in PAP. Additionally, distinct stem cell sources may be associated with the chronic nature of PAP as well as with the development of PPLs.

Lugol Chromoscopy in the Follow-up of Head and Neck Carcinoma.

INTRODUCTION: Lugol is helpful in identifying early second primary tumors (SPTs) during oroscopy and pharyngoscopy, but this technique has not been assessed during follow-up visits with these patients. AIM: The aim of this study is to describe the use of Lugol (a low-cost method) to diagnose SPTs in the oral cavity and oropharynx. METHODS: Patients treated for squamous cell carcinoma of the head and neck were randomly assigned to two groups. Group A was examined with routine oroscopy and pharyngoscopy without Lugol, and Group B was examined with routine oroscopy and pharyngoscopy without stain and with Lugol. A total of 211 patients were included during 4 years. RESULTS: Six oral and oropharynx carcinomas were detected in Group A. Eighteen oral and oropharynx carcinomas were detected in Group B, twelve of which were not seen without chromoscopy but were detected with Lugol. CONCLUSION: Lugol increases the detection of malignant lesions compared to routine examination alone.

An unusual case of four simultaneous eruption cysts in an infant.

Eruption cyst is a benign lesion with favorable prognosis that may occur during the primary or permanent dental eruption. The purpose of this paper is to report the case of an infant who presented with multiple eruption cysts (ECs), describe their clinical and histological features, and discuss the treatment performed. The first ECs occurred around the primary mandibular central incisors when the patient was seven months old, which ruptured spontaneously. Ten months later, the patient presented with simultaneous eruption cysts around the primary mandibular and maxillary first molars, making the child very uncomfortable. Radiographically, all the involved molars had two thirds root formation. Two cysts, both on the right side, were surgically removed, and the other two ruptured spontaneously.

Neuroblastoma-like schwannoma of the lower labial mucosa: a rare morphologic variant of peripheral nerve sheath tumor.

Neuroblastoma-like schwannoma is a rare variant of benign nerve sheath neoplasia, which is histologically characterized by small round neoplastic Schwann cells radially arranged around collagenous cores with a configuration of rosette-like structures. We report the first documented case of neuroblastoma-like schwannoma of the oral cavity in a 26-year-old male patient who presented with swelling in the lower labial mucosa.

Nuclear metallothionein in oral squamous cell carcinoma: clinicopathological parameters and patient survival

Abstract The aim of this study was to identify the immunoexpression of methallothionein in oral squamous cell carcinoma as well as to address the correlation with clinical features, histological grade and patient survival. Samples were collected from 93 patients with tongue squamous cell carcinoma who presented for follow-up. Immunohistochemical expression of methallothionein in all groups was performed. The scoring system has previously been published by Tsurutani in 2005, which is based on intensity and distribution of staining. We used Kappa index to evaluate the degree of observers' agreement under metallothionein immunostaining and histological grade. Associations between methallothionein expression and clinical parameters (age, gender, smoking, tumor size, lymph node metastasis and disease stage) were examined for statistical significance using the chi-squared test. The overall survival rates were estimated by the Kaplan-Meier method and the relationship between protein expression and survival was compared using the log-rank test (p < 0.05). Our results showed no statistically significant association between methallothionein immunostaining and the selected clinicopathological variables. Immunohistochemistry results showed positive nuclear immunostaining for metallothionein in 62,37% (58/93) and negative for metallothionein 37,63% (35/93). The degree of examiners agreement by Kappa varied from substantial to perfect and both metallothionein immunostaining and histological grade were explored. The present study suggests that positive methallothionein expression found in tongue squamous cell carcinoma may not help to predict survival in the analyzed samples, as well as no relation between the protein and histological grade and clinical features was observed. In conclusion, the present study suggests that metallothionein is not associated with tongue squamous cell carcinoma clinicopathological characteristics and aggressiveness.

Hiperplasia Endotelial Papilífera Intravascular Oral: relato de dois casos / Oral intravascular papillary endothelial hyperplasia: two cases report

A hiperplasia endotelial papilífera intravascular (HEPI) é uma lesão vascular não neoplásica, benigna e rara, especialmente em cavidade bucal. O presente artigo relata dois casos com diferentes apresentações clínicas de HEPI, envolvendo o lábio inferior. O primeiro caso se refere a um paciente que apresentava nódulo único submucoso, endurecido, arroxeado e assintomático em mucosa labial inferior. E o segundo se reporta a uma paciente que apresentava aumento de volume assintomático em lábio inferior com a mucosa entumecida e arroxeada desde o fundo de sulco. O exame histológico revelou vasos dilatados com proliferação de células endoteliais arredondadas, associadas a estruturas papilares, de tecido conjuntivo projetadas para o lúmen vascular, associadas a um trombo organizado, no primeiro caso, e a um hemangioma, no segundo. A ausência de células inflamatórias, atipia e necrose celular excluíram outras lesões vasculares, sendo o diagnóstico final de HEPI. O prognóstico da HEPI é excelente, uma vez que recidivas são raramente relatadas. A HEPI pode ser incluída no diagnóstico diferencial clínico de lesões labiais únicas, arroxeadas e endurecidas. E por caracterizarse histologicamente por uma proliferação de células endoteliais, é importante estabelecer o diagnóstico diferencial com o angiossarcoma, uma lesão de tratamento mais agressivo e pior prognóstico... (AU)

Intravascular papillary endothelial hyperplasia (IPEH) is a nonneoplastic vascular benign and rare lesion, especially in oral cavity. This article reports two cases of IPEH, with different clinical presentation, involving the inferior lip. The first case refers to a patient presenting a single submucosal indurated purplish and asymptomatic nodule in the lower labial mucosa. And the second, to a patient presenting an asymptomatic increase in the lower lip associated with a swelling and purplish oral mucosa. Histological examination showed dilated vessels with rounded endothelial cells proliferation associated with papillary structures of connective tissue projected to vascular lumen, associated with an organized thrombus in first case and a hemangioma in the second. The absence of inflammatory cells, cytologic atypia and necrosis excluded other vascular lesions, being the final diagnosis of IPEH. The prognosis of IPEH is excellent since recurrences are rarely reported. Isolated purplish and indurated labial lesions can include the IPEH as a possible clinical hypothesis. And, since is histologically characterized by a proliferation of endothelial cells, is crucial the establishment of the histological differential diagnosis with angiosarcoma, which requires a more aggressive treatment and has worse prognosis... (AU)

Chondroblastic osteosarcoma mimicking periapical abscess

Abstract Lesions of non-endodontic origin may mimic periapical abscess. Osteosarcoma is a rare malignant lesion. Case report The present report describes a case of chondroblastic osteosarcoma in the periapical region of teeth #29, #30, and #31 of an 18-year-old male. Clinical history showed self-reported discomfort in the right posterior gingiva for over a month. Physical examination showed a small expansion and redness of the right mandibular buccal and lingual cortical plates, but no signs of pain or inflammation were observed. All the teeth responded positively to pulp sensibility. Periapical and panoramic radiographs showed slight periapical radiolucency in the roots of teeth #29 and #30, clear periodontal ligament space widening, and evident loss of lamina dura. Incisional biopsy was performed, and based on microscopic findings the diagnosis of chondroblastic osteosarcoma was confirmed. Conclusions Non-endodontic diseases associated with tooth root apex, such as chondroblastic osteosarcoma, should be included in differential diagnosis of jaw lesions that resemble periapical abscess.