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.

A rare case of mucoepidermoid carcinoma ex-pleomorphic adenoma of the hard palate.

Carcinoma Ex-Pleomorphic Adenoma (CExPA) is a salivary gland carcinoma derived from a primary or recurrent benign pleomorphic adenoma (PA) extremely rare in minor salivary glands. In this paper, we report the case of a male afrodescendant patient, 37 years old, presenting a palatal irregular nodular lesion with approximately 3.5 cm diameter. The lesion had over two years of evolution, but started growing faster and presenting pain and ulceration in the last two months. The incisional biopsy revealed a typical pleomorphic adenoma with focal areas of nests of epidermoid and mucous cells, as well as microcyst formations, resembling the mucoepidermoid carcinoma (MEC). Immunohistochemical analysis revealed positivity for CK7, CK13, CK 14, p63 and Ki67 (about 30%), whereas α-SMA was restricted to the PA component. The diagnosis was CExPA (MEC-type). A discussion on the histopathological and immunohistochemical criteria for differential diagnosis of CExPA is provided in this work, hoping to contribute to a better knowledge and understanding of this rare malignant tumor. Key words:Salivary gland neoplasms, pleomorphic adenoma, adenocarcinoma, mucoepidermoid carcinoma, pathology, differential diagnosis.

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.

Secretory carcinoma ex pleomorphic adenoma of the submandibular gland: An immunohistochemical study.

Male patient 60-year-old was referred from another service for expert review of a lesion in the submental region. Pathological review revealed morphological features compatible with salivary gland Secretory carcinoma (SC) in cervical lymph node. The patient underwent removal of the left submandibular gland, left neck dissection and biopsy of left labial commissure region. Anatomopathological examination was observed tumor cells arranged in a solid and ductal/cystic pattern, with abundant droplets of secreted eosinophilic material within these structures and extensive hyalinized area, which presented few cells arranged in a ductal pattern. It was possible to observe the presence of extracapsular extension of neoplastic cells > 6 mm, base on this aspects, Carcinoma ex pleomorphic adenoma was suspected. Immunohistochemical panel showed positivity for mammaglobin, s100, CK7, and adipophilin and negativity for myoepithelial markers and PAS in SC cells. The myoepithelial markers showed positivity for residual cellsin hyalinized area, corresponding to residual Pleomorphic adenoma (PA). In view of these findings, the diagnosis of Secretory carcinoma ex pleomorphic adenoma (SCXPA) was established.

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.

CTNNB1 and APC mutations in odontogenic carcinoma with dentinoid.

The purpose of the present study is to report 2 cases of odontogenic carcinoma with dentinoid, a rare low-grade odontogenic carcinoma associated with facial deformity and bone loss, and to investigate the presence of pathogenic mutations in these samples. By using a next-generation sequencing approach, we sequenced a panel of 50 oncogenes and tumor suppressor genes commonly mutated in human cancer. Microscopic features of both cases revealed solid areas of malignant odontogenic tumor with a large amount of dentinoid material. We identified pathogenic mutations in the genes CTNNB1 and APC, both of which are part of the Wnt-signaling pathway. Consistent with Wnt-signaling activation, both tumors showed strong ß-catenin accumulation in the cytoplasm and in the nuclei. The molecular profile of odontogenic carcinoma with dentinoid may help in its diagnosis, as well as in the identification of potential molecular targets for therapy in the future.

Immunohistochemical expression of RANKL in oral giant cell lesions is predictive of aggressiveness.

The aim of this study was to evaluate the immunohistochemical expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and of osteoprotegerin (OPG), important proteins correlated with osteoclastogenesis, in central giant cell lesions (CGCL) and peripheral giant cell lesions (PGCL) and to compare their expression with the histological and clinical parameters for quantification of multinucleated giant cells (MGC) and their nuclei, lesion size, and recurrences. Twenty cases of each lesion type were selected to quantify the number of MGCs and nuclei/mm2 of connective tissue. The immunoreactivity of RANKL and OPG was expressed as a percentage of the marked area in the stroma. Clinical data were collected from pathoanatomical and medical reports. No statistical differences were found for the number of MGCs (p = 0.24) between PGCL and CGCL, but the number of nuclei within the MGCs was higher in CGCL (p = 0.01). RANKL expression was higher in CGCL than in PGCL (p = 0.04) and all recurrent lesions showed higher RANKL and OPG expressions than nonrecurrent lesions. We report higher RANKL expression and a greater number of nuclei in CGCL, which may explain the difference in clinical behaviour between these lesions and their pathogenesis.

Immunohistochemical expression of RANKL in oral giant cell lesions is predictive of aggressiveness

Abstract The aim of this study was to evaluate the immunohistochemical expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and of osteoprotegerin (OPG), important proteins correlated with osteoclastogenesis, in central giant cell lesions (CGCL) and peripheral giant cell lesions (PGCL) and to compare their expression with the histological and clinical parameters for quantification of multinucleated giant cells (MGC) and their nuclei, lesion size, and recurrences. Twenty cases of each lesion type were selected to quantify the number of MGCs and nuclei/mm2 of connective tissue. The immunoreactivity of RANKL and OPG was expressed as a percentage of the marked area in the stroma. Clinical data were collected from pathoanatomical and medical reports. No statistical differences were found for the number of MGCs (p = 0.24) between PGCL and CGCL, but the number of nuclei within the MGCs was higher in CGCL (p = 0.01). RANKL expression was higher in CGCL than in PGCL (p = 0.04) and all recurrent lesions showed higher RANKL and OPG expressions than nonrecurrent lesions. We report higher RANKL expression and a greater number of nuclei in CGCL, which may explain the difference in clinical behaviour between these lesions and their pathogenesis.

Clinicopathologic analysis of 14 cases of odontogenic myxoma and review of the literature.

BACKGROUND: Odontogenic myxoma is a rare benign neoplasm that originates from odontogenic ectomesenchyme. There is no standard of care and recurrences are frequent after conservative surgical procedures. MATERIAL AND METHODS: A retrospective study conducted at a single cancer center, with analysis of medical records of all patients diagnosed with odontogenic myxoma from 1980 to 2010, along with a literature review. RESULTS: There were 14 patients with diagnosis of odontogenic myxoma (OM). Most patients were female (78.6%) and Caucasian (100%), with ages ranging from 7 to 51 years (21.6 ± 11.6 years). The time period between the first symptom and first consultation ranged from 0 to 60 months (19.4 ± 19.97 months). The most frequent complaints were increased local volume or failure to tooth eruption. The most common tumor site was the mandible (11 cases, 78.5%). About radiological findings, most lesions were multilocular (9 cases, 64.3%) and with imprecise limits (12 cases, 85.7%). Surgery was performed in all cases and curettage was the most applied technique (10 cases, 71.4%). Three patients underwent mandibulectomy and complex reconstructions including iliac crest microvascular flap. Three patients had postoperative complications and 4 had local recurrences of the tumor. The follow up time ranged from 12 to 216 months (112 ± 70.8 months). All patients are without clinical and radiographic evidence of disease. CONCLUSIONS: OM is a locally aggressive and rare tumor. There is no gold standard surgical management and the therapeutic decision should be individualized taking into account the characteristics and extension of the tumor. Key words:Mandible, myxoma, odontogenic, odontogenic tumor.

Tissue integrity, costs and time associated with different agents for histological bone preparation.

The selection of an appropriate demineralizing solution in pathology laboratories depends on several factors such as the preservation of cellularity, urgency of diagnostic and financial costs. The aim of this study was to test different decalcification bone procedures in order to establish the best value of these in formalin-fixed and paraffin-embedded samples. Femurs were removed from 13 adult male Wistar rats to obtain 130 bone disks randomly divided into five groups that were demineralized in different concentrations of nitric acid (Group I); formic acid (Group II); acetic acid (Group III); EDTA, pH7.4 (Group IV) and Morsés solution (Group V). Serial, 3-µm-thick sections were obtained and stained with hematoxylin-eosin to calculate the percentage of osteocyte-occupied lacunae. The sections were also stained with Masson's trichrome in conjunction with picrosirius red under polarized light followed by a semi-quantitative analysis to verify the adjacent muscle-to-bone integrity and preservation of collagen fibres. The highest percentage of osteocyte-occupied lacunae was found with 10% acetic acid solution (95.64 ± 0.95%) and Group I (nitric acid) demanded the shorter time (0.8-5.7days). Of all solutions, 5% nitric acid incurred the lowest cost to achieve complete demineralization compared with other solutions (p < .001). Group IV (EDTA) had the highest integrity of muscle and collagen type I and III (P < 0.01). Demineralization with 10% acetic acid was the most effective at preserving bone tissue, while 5% EDTA was the best at maintaining collagen and adjacent muscle to bone. In conclusion, nitric acid at 5% showed the most efficient result as it balanced both time and cost as a demineralizing solution.

CD1a+ and CD83+ Langerhans cells are reduced in lower lip squamous cell carcinoma.

BACKGROUND: Actinic cheilitis (AC) is a potentially malignant lesion diagnosed in the lip of patients chronically exposed to the sun that may give rise to a fully invasive lower lip squamous cell carcinoma (LLSCC). It is known that ultraviolet radiation causes dendritic cells (DCs) depletion in the epidermis, but the role of this cellular population in lip cancer progression remains uncertain. Therefore, this study investigated the distribution of DCs in normal, dysplastic and neoplastic tissues of the lower lip. METHODS: Thirteen cases of lower lip mucocele, 42 of ACs and 21 of LLSCC were retrieved and original diagnoses confirmed by two oral pathologists, who further classified ACs as low- and high-risk lesions. Immunoreactions against CD1a and CD83 identified immature and mature DCs, respectively. RESULTS: Immature CD1a+ Langerhans cells (LCs) were significantly decreased in LLSCC when compared to morphologically normal (P < 0.009) and dysplastic epitheliums (P < 0.003), whereas mature CD83+ LCs were significantly decreased in LLSCC when compared to normal epithelium (P = 0.038). There was no significant difference between low- and high-risk ACs regarding CD1a+ and CD83+ LCs (P > 0.05), but ACs demonstrated a lower concentration of CD1a+ LCs than normal epithelium (P < 0.009). There was no significant difference in the distribution of CD1a+ and CD83+ interstitial dendritic cells (IDCs) in the connective tissue among the studied groups (P > 0.05). CONCLUSION: These results suggest that depletion of epithelial LCs, but not IDCs in the connective tissue, would represent an important step for lip cancer development.

Cellular Proliferation Index between Carcinoma Ex-Pleomorphic Adenoma and Pleomorphic Adenoma.

Carcinoma ex pleomorphic adenoma (CXPA) has been considered an interesting model of carcinogenesis, presenting various histological subtypes and invasiveness phase. The objective was to determine the proliferative index of CXPA and comparing to pleomorphic adenoma (PA). Thirty six cases of CXPA (36 PA) and 22 areas of PA in CXPA (residual PA) were studied by Ki-67 expression. All CXPA cases were classified according to invasiveness phase (intracapsular, minimally and frankly invasive) and histopathological subtypes. Data was statistically analyzed by Wilcoxon, Mann-Whitney and Kruskal-Wallis tests. CXPA included 5 intracapsular, 9 minimally invasive and 22 frankly invasive cases. Fifteen cases corresponded to salivary duct carcinoma, 7 to adenocarcinoma NOS, 7 myoepithelial, 5 epithelial-myoepithelial, one case of squamous cell and one case of sarcomatoid carcinoma. The Ki-67 index of PA and residual PA were significantly lower than CXPA. Intracapsular and minimally invasive showed smaller proliferative index than frankly invasive. Considering the subtypes of CXPA, there was not a statistic difference among them. Ki-67 is a useful marker in the differential diagnosis of PA and CXPA, even when in the early invasive phase.

Cellular Proliferation Index between Carcinoma Ex-Pleomorphic Adenoma and Pleomorphic Adenoma

Carcinoma ex pleomorphic adenoma (CXPA) has been considered an interesting model of carcinogenesis, presenting various histological subtypes and invasiveness phase. The objective was to determine the proliferative index of CXPA and comparing to pleomorphic adenoma (PA). Thirty six cases of CXPA (36 PA) and 22 areas of PA in CXPA (residual PA) were studied by Ki-67 expression. All CXPA cases were classified according to invasiveness phase (intracapsular, minimally and frankly invasive) and histopathological subtypes. Data was statistically analyzed by Wilcoxon, Mann-Whitney and Kruskal-Wallis tests. CXPA included 5 intracapsular, 9 minimally invasive and 22 frankly invasive cases. Fifteen cases corresponded to salivary duct carcinoma, 7 to adenocarcinoma NOS, 7 myoepithelial, 5 epithelial-myoepithelial, one case of squamous cell and one case of sarcomatoid carcinoma. The Ki-67 index of PA and residual PA were significantly lower than CXPA. Intracapsular and minimally invasive showed smaller proliferative index than frankly invasive. Considering the subtypes of CXPA, there was not a statistic difference among them. Ki-67 is a useful marker in the differential diagnosis of PA and CXPA, even when in the early invasive phase.

Carcinoma ex adenoma pleomorfo (CXAP) tem sido considerado um interessante modelo de carcinogênese, apresentando vários subtipos histológicos e fases de invasividade. Determinar o índice proliferativo de CXAP e compará-lo ao adenoma pleomorfo (AP). e seis casos de CXAP, 36 AP, e 22 áreas de AP em CXAP (AP residual) foram estudadas através da expressão de Ki-67. Todos os casos de CXAP foram classificados de acordo com a fase de invasividade (intracapsular, minimamente invasivo e francamente invasivo) e de acordo com os diversos subtipos histopatológicos. Os dados foram estatisticamente analisados através dos testes Wilcoxon, Mann-Whitney e Kruskal-Wallis. O grupo de CXAP era formado por 5 intracapsulares, 9 minimamente invasivos e 22 francamente invasivos. Quinze casos corresponderam a carcinoma de ducto salivar, 7 a adenocarcinoma nos, 7 a carcinoma mioepitelial, 5 a carcinoma epitelial-mioepitelial, 1 a carcinoma epidermoide e 1 a carcinoma sarcomatóide. Os índices de Ki-67 de AP e AP residual foram significativamente menores que o encontrado em CXAP. Os casos intracapsulares e minimamente invasivos mostraram índices proliferativos menores que os francamente invasivos. Considerando os subtipos histológicos de CXAP, não houve diferença estatística entre eles. Ki-67 é um marcador útil no diagnóstico diferencial de AP e CXAP, mesmo quando o carcinoma está em fase precoce de invasividade.

Maxillary desmoplastic fibroma with initial symptoms suggestive of sinusitis.

Desmoplastic fibroma (DF) is a benign intra-osseous neoplasm characterized by the formation of abundant collagen fibers. It arises most commonly in the jaws and exhibits local aggressiveness and high recurrence rates after local resection. An uncommon case of expansive DF involving the right maxilla, maxillary sinus, and inferior orbital wall of a 49-year-old man whose initial symptoms were similar to acute sinusitis is presented, and the criteria for diagnosis and clinical management are discussed.

Carcinoma ex-pleomorphic adenoma of upper lip showing copy number loss of tumor suppressor genes.

BACKGROUND: Carcinoma ex-pleomorphic adenoma (CXPA) is a malignant salivary gland tumor that arises rarely in the minor salivary glands. Although the etiology of CXPA remains unclear, the role of some tumor suppressor genes and oncogenes in CXPA is documented; however, other genes still need to be studied. STUDY DESIGN AND OBJECTIVE: An uncommon case of CXPA involving the upper lip is presented, which was analyzed by a panel of tumor suppressor genes by multiplex ligation-dependent probe amplification. RESULTS: The genes investigated in this study, a loss of copy number was detected for CASP8, CD44, CDH1, DAPK1, ESR1, RASSF1, and TP73. Immunohistochemical reactions for the validation of some of these results showed negativity for CD44, RASSF1, and p73. CONCLUSION: A loss of copy number of the genes CD44, RASSF1, and TP73 may contribute to the carcinogenesis of CXPAs.

Reactive post-radiotherapy bone formation in the maxilla.

OBJECTIVE: High-dose radiation therapy affects bone metabolism, and therefore post-radiotherapy bone formation is an uncommon finding. This case describes an unusual ossification in the maxillary region identified after head and neck radiotherapy. RESULTS: A 45-year-old female patient was submitted to maxillary surgical resection and orbital exenteration due to squamous cell carcinoma. Radiotherapy post-surgery was performed because of compromised surgical margins. After 4 months of the conclusion of radiotherapy, the patient presented a bone exposition at surgical site. Surprisingly, the oral examination and computed tomography revealed a new formation of the right palatine vault and bone formation filling the nasal and orbital cavity. The incisional biopsy discarded residual disease or osteoradionecrosis and showed normal tissue. CONCLUSIONS: To the best of the authors' knowledge, this is the first case of wide bone formation as an early effect of head and neck radiotherapy.

Unicystic ameloblastoma mimicking apical periodontitis: a case series.

INTRODUCTION: The purpose of this study was to describe a series of unicystic ameloblastomas (UAs) that presented clinical and radiographic similarities to apical periodontitis in order to call the attention of clinicians to the fact that several different diseases are able to mimic endodontic periapical lesions. METHODS: A retrospective clinicopathological analysis of 5 patients who had periapical lesions in the mandible initially diagnosed as apical periodontitis but with a final histologic diagnosis of UAs is presented. RESULTS: Three men and 2 women with a mean age of 26.4 years presented lesions involving the posterior mandible. No patient reported pain, and 3 patients showed pulp vitality of the involved teeth. Radiographically, all lesions presented periapical well-defined radiolucencies, ranging from 2 to 3 cm in diameter, and 3 cases presented root resorption. Endodontic therapy was applied in 2 patients who were referred to our clinics because of a lack of involution of the periapical lesions. All patients were submitted to periapical surgical curettage and histologically diagnosed as UA. After a mean follow-up of 45.6 months, all patients are well without signs of recurrence. CONCLUSIONS: UA may involve the periapical area of teeth, mimicking an inflammatory lesion of endodontic origin. The diagnosis of periapical lesions should be determined based on clinical and radiographic aspects. Recalcitrant lesions should be surgically explored and submitted to histologic evaluation. The early diagnosis of nonendodontic lesions mimicking apical periodontitis such as UA may prevent unnecessary endodontic treatment and wide surgical resections.

Oral pigmented lesions: Clinicopathologic features and review of the literature.

Diagnosis of pigmented lesions of the oral cavity and perioral tissues is challenging. Even though epidemiology may be of some help in orientating the clinician and even though some lesions may confidently be diagnosed on clinical grounds alone, the definitive diagnosis usually requires histopathologic evaluation. Oral pigmentation can be physiological or pathological, and exogenous or endogenous. Color, location, distribution, and duration as well as drugs use, family history, and change in pattern are important for the differential diagnosis. Dark or black pigmented lesions can be focal, multifocal or diffuse macules, including entities such as racial pigmentation, melanotic macule, melanocytic nevus, blue nevus, smoker's melanosis, oral melanoacanthoma, pigmentation by foreign bodies or induced by drugs, Peutz-Jeghers syndrome, Addison's disease and oral melanoma. The aim of this review is to present the main oral black lesions contributing to better approach of the patients.