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.

Hybrid Neurofibroma/Schwannoma of the Oral Cavity: A Rare Case Report and Literature Review.

Hybrid peripheral nerve sheath tumors show combined features of more than one type of conventional benign peripheral nerve sheath tumors. There are few cases reported of hybrid peripheral nerve sheath tumors in the head and neck region. A 68-year-old female patient was referred for evaluation of an oral swelling lasting five years. Intraoral examination revealed a small mobile nodule located in the lower vestibule. The patient underwent excisional biopsy and microscopic evaluation showed typical features of neurofibroma enclosing areas with palisading nuclei compatible with Antoni A pattern, which are seen in schwannomas. These regions showed strong and diffuse immunoreactivity for S100 protein and moderate positivity in the neurofibroma area. CD34 was positive in the neurofibroma area and entrapped axons were positive for neurofilament. The final diagnosis was oral hybrid neurofibroma-schwannoma tumor. Hybrid peripheral nerve sheath tumors, although extremely rare, may arise within the oral cavity. To the best of our knowledge, this is the first neurofibroma-schwannoma tumor reported in the oral cavity. Recognizing hybrid peripheral nerve sheath tumors as a distinct clinicopathological entity is important because they may also be associated with syndromic disorders.

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.

The need for communication between clinicians and pathologists in the context of oral and maxillofacial diseases.

Good communication between clinicians and pathologists is a vital element in the diagnostic process, and poor communication can adversely affect patient care. There is a lack of research about communication in diagnostic oral and maxillofacial pathology. This narrative review explores different aspects of the quality of communication between clinicians and oral pathologists, with a focus on the diagnosis of oral and maxillofacial diseases. An electronic search was carried out in MEDLINE through the PubMed, Scopus, and Embase databases up to April 2021. No studies reporting communication, its adequacy or the required skills between clinicians and pathologists in oral diagnosis were found. According to studies published in medicine, strategies for improving communication skills include clinician-pathologist collaboration; a well-formatted, clear and thorough report; training in communication skills; and patient-centered care. Further studies evaluating the current practices and quality in oral and maxillofacial pathology are required to identify barriers and encourage optimal communication to facilitate diagnosis, as well as patient safety.

Oncocytic Lipoadenoma: Report of 3 Rare Cases Involving the Parotid Gland, Including a Synchronous Presentation With Paraganglioma of the Right Carotid Bifurcation and Literature Review.

Oncocytic lipoadenoma (OL) is a rare salivary gland tumor characterized by the presence of oncocytic cells and mature adipose tissue. To date, only 30 cases of OL have been reported in the English-language literature. We present 3 additional OL cases involving the parotid, including a synchronous presentation with paraganglioma of the right carotid bifurcation. Microscopically, both the OLs were composed of a mixed population of oncocytes and adipocytes in varying proportions surrounded by a thin, connective tissue fibrous capsule. Oncocytes were positive for pan-cytokeratins (CKs) AE1/AE3, epithelial membrane antigen, CK5, CK7, CK14, CK18, and CK19. Calponin, p63, alpha-smooth muscle actin, and carcinoembryonic antigen were negative. Vimentin and S-100 protein were positive only in adipose cells. Despite distinctive morphologic features, OL is often misdiagnosed, given its rarity. We hope to contribute to surgeons' and pathologists' awareness and knowledge regarding the existence of this tumor and provide adequate management through conservative surgical excision.

The need for communication between clinicians and pathologists in the context of oral and maxillofacial diseases

Abstract Good communication between clinicians and pathologists is a vital element in the diagnostic process, and poor communication can adversely affect patient care. There is a lack of research about communication in diagnostic oral and maxillofacial pathology. This narrative review explores different aspects of the quality of communication between clinicians and oral pathologists, with a focus on the diagnosis of oral and maxillofacial diseases. An electronic search was carried out in MEDLINE through the PubMed, Scopus, and Embase databases up to April 2021. No studies reporting communication, its adequacy or the required skills between clinicians and pathologists in oral diagnosis were found. According to studies published in medicine, strategies for improving communication skills include clinician-pathologist collaboration; a well-formatted, clear and thorough report; training in communication skills; and patient-centered care. Further studies evaluating the current practices and quality in oral and maxillofacial pathology are required to identify barriers and encourage optimal communication to facilitate diagnosis, as well as patient safety.

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.

Ossifying fibromyxoid tumor of the oral cavity: rare case report and long-term follow-up

Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal soft tissue benign neoplasm with an uncertain line of differentiation, which arises most frequently in extremities. The head and neck region involvement is uncommon, with only ten intraoral cases published in the English-language literature. One additional case of OFMT is reported here, including a literature review of intraoral reported cases. A 45-year-old female patient presented a painless nodule involving the buccal mucosa of approximately two years duration, measuring nearly 1.3 cm in maximum diameter. The main histopathological features include ovoid to round cells embedded in a fibromyxoid matrix with a perpheral shell of lamellar bone. Immunohistochemically, the tumor showed immunoreactivity for vimentin and S100. No recurrence has been detected after 7 years of follow-up.

Clinicopathologic study of 6 cases of epithelioid osteoblastoma of the jaws with immunoexpression analysis of FOS and FOSB.

OBJECTIVE: The aim of this study was to describe the clinicopathologic features of a series of gnathic epithelioid osteoblastomas. As high levels of Proto-oncogene c-Fos proteins resulting from FOS-FOSB translocation were recently demonstrated in osteoblastomas, we also evaluated the immunoexpression of these proteins. STUDY DESIGN: Records of all cases of epithelioid osteoblastoma of the jaws were retrieved from oral pathology services, and their clinicopathologic and immunohistochemical data were collected. Immunohistochemistry was also performed by using anti-FOS and anti-FOSB antibodies. RESULTS: Six cases of epithelioid osteoblastomas were obtained, 4 in men and 2 in women, and they were mainly located in the posterior body of the mandible (n = 4). Radiographically, the tumors showed mixed radiolucent and radiopaque images, most with poorly defined margins. Microscopically, large epithelioid cells with eccentrically located nuclei predominated among osteoid and immature bone trabeculae. Sharp delineation from adjacent normal bone was observed in all cases. FOS immunostaining was diffuse and strong in the cytoplasm and nucleus of neoplastic cells in all cases, whereas FOSB was only focally positive, with few epithelioid osteoblasts showing nuclear staining. CONCLUSIONS: Although epithelioid osteoblastomas of the jaws are locally aggressive, widespread metastasis does not occur, and, as with conventional osteoblastomas, there is wide expression of the FOS protein.

Spindle cell carcinoma of the maxillary sinus with extension to the oral cavity

Spindle cell carcinoma (SCC) is a rare variant of squamous cell carcinoma characterized by elongated and pleomorphic epithelial cells that resemble a sarcoma. Due to its rareness, and histological resemblance to various sarcomas, the diagnosis of this neoplasia is challenging. Herein we present the case of an 82-year-old female with a polypoid, ulcerated, soft tissue mass located on the left side of the maxilla. The tomographic examination showed a hyperdense mass that infiltrated the orbital cavity, ethmoidal cells, middle and lower nasal concha, maxillary sinus, zygomatic arch, and mandibular ramus on the left side. Histopathologically, the tumor was composed of spindle cells that were sarcomatous in appearance, with aberrant mitosis, along with a group of pleomorphic cells with a more epithelioid and hyperchromatic appearance on a stroma of densely vascularized fibrous tissue. The immunohistochemistry panel used to determine the lineage of the tumor rendered the diagnosis of SCC. The diagnosis of SCC is challenging to the pathologist since its morphology can resemble a sarcoma. Thus, immunohistochemistry is a valuable resource to support the diagnosis. We propose that SCC should be considered when examining a biphasic neoplasm with the aforementioned histological characteristics and markers.

Intraoral EBV-positive sporadic Burkitt lymphoma in an elderly patient with bilateral presentation

Sporadic Burkitt lymphoma (SBL) is a variant of Burkitt lymphoma that occurs worldwide, affecting mainly children and young adults. Association with Epstein-Barr virus (EBV) can be identified in approximately 20-30% of cases. Herein we described a case of a 63-year-old male presenting intraoral bilateral mandibular swelling, subjacent to fixed dental prosthesis, with one month of duration. Incisional biopsies were performed, and after two days, the patient was hospitalized due to malaise and breathing difficulty, and died after a week when an abdominal tumor was detected. The mandibular biopsies revealed a diffuse proliferation of medium-sized monomorphic atypical lymphoid cells exhibiting numerous mitoses and areas of "starry-sky" pattern. The tumor showed immunohistochemical positivity for CD20, CD10, Bcl-6, and Ki-67 (≈ 100%); it was negative for CD3, Bcl-2, Vs38c, and MUM-1. Positivity for EBV was found by in situ hybridization. The final diagnosis was intraoral SBL positive for EBV. Clinical, morphological and molecular criteria are necessary for the correct diagnosis of aggressive B-cell neoplasms positive for EBV in elderly patients.

Diffuse cutaneous leishmaniasis with oral involvement in a patient of Northern Mexico.

Diffuse cutaneous leishmaniasis is a rare chronic infectious disease, associated with Leishmania mexicana and L. amazonensis, presenting as multiple non-ulcerative painless nodules, with a tendency to relapse soon after treatment. We report a case of a 56-year-old Mexican woman exhibiting nodular lesions, plaques, crusts and scars involving the whole body. A solitary nodule was present at the junction between hard and soft palates. Diffuse cutaneous leishmaniasis is a disfiguring disease resulting in severe scarring if untreated.

Glomus Tumor of the Oral Cavity: Report of a Rare Case and Literature Review.

Glomus tumor is a benign neoplasm composed of a perivascular proliferation of glomic cells that resembles the normal glomus body. Usually, it appears as a solitary, symptomatic small blue-red nodule, located in the deep dermis or subcutis of upper or lower extremities of young to middle-aged adults. Cases affecting the oral cavity are very rare, with only 23 well-documented cases reported in the English-language literature. Herein, we present a rare case of glomus tumor of the upper lip, and review the literature of cases involving the mouth.

Leiomyomatous Hamartomas of the Oral Cavity: Clinicopathological and Immunohistochemical Features of 4 Cases and Literature Review.

Objective. To present 4 new cases of oral leiomyomatous hamartomas (OLH), describing its clinical, microscopical, and immunohistochemical features, and a literature review. Methods. The OLH cases were retrieved from the files of 2 Brazilian and 1 Peruvian oral pathology services. Clinical data were obtained from the pathology reports. Microscopical features were reviewed, and immunohistochemical reactions were performed. A review of the English-language literature about OLH was done. Results. The sample was composed of 3 females (4-, 10-, and 15-year-old) and 1 male (3-year-old). Three cases affected the dorsum of the tongue and one the incisive papilla, and all presented sessile or pedunculated smooth nodules. Microscopically, the lesions were composed of varying-size fascicles of smooth muscle fibers in a fibrous connective tissue background. Immunohistochemistry revealed positivity of the smooth muscle bundles for myogenic markers. The English-language literature review revealed 38 OLH cases reported, most were congenital or diagnosed up to 5 years old. The main locations were tongue and anterior maxilla. Conclusions. Although OLH is a rare lesion, it must be considered in the differential diagnosis of midline tongue or maxillary masses in newborns, infants, and youngsters.

Chondroid Tenosynovial Giant Cell Tumor of the Temporomandibular Joint: A Rare Case Report.

Tenosynovial giant cell tumor of diffuse type (TGCT-d) or pigmented villonodular synovitis (PVNS) is a locally aggressive lesion that mostly affects the joints of long bones. Chondroid tenosynovial giant cell tumor (CTGCT) or PVNS with chondroid metaplasia is a rare distinct subset of synovial tumors that has a predilection for the TMJ. We report a rare case of CTGCT in the TMJ, initially misdiagnosed as temporomandibular disorder (TMD). A 51-year-old woman was referred to the surgeon with the chief complaint of TMJ pain for 5 years and a past history of an unsuccessful TMD treatment. Extraoral examination revealed discrete preauricular swelling and restricted mandibular range of motion. Panoramic radiograph and computerized tomography showed destruction of the mandibular fossa and condyle. Histologically, the tumor was composed by large mononuclear cells with prominent eosinophilic cytoplasm and grooved nuclei, small histiocytoid cells, osteoclast-like multinucleated cells, brown pigmentation and areas of chondroid metaplasia. Morphological and immunohistochemical characteristics lead to the final diagnosis of CTGCT. The rarity of CTGCT could be attributed to the lack of recognition of this lesion, with cases diagnosed as chondroblastomas, synovial chodromatosis and chondrosarcoma. The patient received immediate reconstruction and recurrence was found 22 months after initial intervention. TGCT-d and CTGCT of the TMJ can present similar symptoms to TMD, but clinicians must distinguish both lesions by complete examination, imaging and, when necessary, histopathologic evaluation.

Chondroid Tenosynovial Giant Cell Tumor of the Temporomandibular Joint: A Rare Case Report

Abstract Tenosynovial giant cell tumor of diffuse type (TGCT-d) or pigmented villonodular synovitis (PVNS) is a locally aggressive lesion that mostly affects the joints of long bones. Chondroid tenosynovial giant cell tumor (CTGCT) or PVNS with chondroid metaplasia is a rare distinct subset of synovial tumors that has a predilection for the TMJ. We report a rare case of CTGCT in the TMJ, initially misdiagnosed as temporomandibular disorder (TMD). A 51-year-old woman was referred to the surgeon with the chief complaint of TMJ pain for 5 years and a past history of an unsuccessful TMD treatment. Extraoral examination revealed discrete preauricular swelling and restricted mandibular range of motion. Panoramic radiograph and computerized tomography showed destruction of the mandibular fossa and condyle. Histologically, the tumor was composed by large mononuclear cells with prominent eosinophilic cytoplasm and grooved nuclei, small histiocytoid cells, osteoclast-like multinucleated cells, brown pigmentation and areas of chondroid metaplasia. Morphological and immunohistochemical characteristics lead to the final diagnosis of CTGCT. The rarity of CTGCT could be attributed to the lack of recognition of this lesion, with cases diagnosed as chondroblastomas, synovial chodromatosis and chondrosarcoma. The patient received immediate reconstruction and recurrence was found 22 months after initial intervention. TGCT-d and CTGCT of the TMJ can present similar symptoms to TMD, but clinicians must distinguish both lesions by complete examination, imaging and, when necessary, histopathologic evaluation.

Resumo Tumor de células gigantes tenossinovial do tipo difuso (TCGT-d) ou sinovite vilonodular pigmentada (SVP) é uma lesão localmente agressiva que afeta principalmente as articulações dos ossos longos. Tumor de células gigantes tenossinovial condroide (TCGTC) ou SVP com metaplasia condroide é um tipo distinto e raro de tumor sinovial que tem a predileção pela articulação temporomandibular (ATM). Nós relatamos um caso raro de TCGTC da ATM, inicialmente diagnosticado, equivocadamente, como disfunção temporomandibular (DTM). Uma mulher de 51 anos foi encaminhada ao cirurgião com a queixa principal de dor na ATM por 5 anos, e uma história de tratamento de DTM sem sucesso. O exame extrabucal revelou discreto aumento de volume preauricular e movimentação mandibular restrita. A radiografia panorâmica e a tomografia computadorizada evidenciaram destruição da fossa mandibular e côndilo. Histologicamente, o tumor era composto por células mononucleares grandes, com amplo citoplasma eosinofílico e núcleo sulcado, pequenas células histiocitoides, células multinucleadas semelhantes a osteoclastos, pigmentação acastanhada e áreas de metaplasia condroide. As características morfológicas e imuno-histoquímicas levaram ao diagnóstico final de TCGTC. A raridade desta lesão pode estar associada ao seu não reconhecimento, sendo casos diagnosticados como condroblastoma, condromatose sinovial ou condrossarcoma. A paciente recebeu reconstrução imediata e recorrência foi observada 22 meses após a intervenção inicial. TCGT-d e TCGTC da ATM podem apresentar sintomas similares à DTM, mas os clínicos devem diferenciar ambas as lesões por meio do exame clínico completo, exames de imagem e, quando necessário, avaliação histopatológica.

Prognostic significance of hMSH2, hMSH3, and hMSH6 expression in ameloblastoma.

OBJECTIVE: The aim of this study was to investigate hMutS proteins in developing human tooth, ameloblastomas, and ameloblastic carcinoma and to determine whether the expression of these proteins has any prognostic potential. STUDY DESIGN: Ten cases of developing human tooth, 39 ameloblastomas, and 2 ameloblastic carcinomas were used to determine the distribution of the proteins during the process of carcinogenesis. Simultaneously, another sample of 73 ameloblastomas was arranged in tissue microarray, and their clinical, microscopic, and radiographic features; treatment outcome; presence of BRAF-V600E mutation; and follow-up data were assessed to determine the prognostic relevance of the expression of hMutS (hMSH2, hMSH3, hMSH6) and Ki-67. hMSH2 and hMSH6 were significantly downexpressed in ameloblastomas (P = .0059) compared with developing human tooth (P < .0001). RESULTS: hMSH2, hMSH3 expression were significantly associated with BRAF-V600E mutation (P < .05). Simultaneous overexpression of hMutS was associated with recurrence (P = .035); however, these did not predict the disease-free survival of patients (P > .05). CONCLUSIONS: hMutS proteins are downregulated in ameloblastoma; moreover, simultaneous overexpression of these proteins in ameloblastoma was associated with recurrence but did not predict disease-free survival.

Furuncular Myiasis Affecting the Lower Lip of a Young Patient.

Furuncular myiasis is a parasitic infection caused by the larvae of Dipteran insects after penetrating healthy skin, causing an erythematous nodule with a central pore. Additionally, the patient may feel a sensation of movement and intermittent pain. Furuncular myiasis affecting the oral and perioral region is rare, usually leading to misdiagnosis. This paper describes a rare case of furuncular myiasis in a 20-year-old healthy male patient who presented an erythematous nodule in the lower lip. An exploratory surgery was indicated for both diagnostic and curative purposes, with successful healing observed in the following appointment. After 3 years of follow-up, the patient is recovered, with no clinical signs or symptoms of the disease.

Furuncular Myiasis Affecting the Lower Lip of a Young Patient

Abstract Furuncular myiasis is a parasitic infection caused by the larvae of Dipteran insects after penetrating healthy skin, causing an erythematous nodule with a central pore. Additionally, the patient may feel a sensation of movement and intermittent pain. Furuncular myiasis affecting the oral and perioral region is rare, usually leading to misdiagnosis. This paper describes a rare case of furuncular myiasis in a 20-year-old healthy male patient who presented an erythematous nodule in the lower lip. An exploratory surgery was indicated for both diagnostic and curative purposes, with successful healing observed in the following appointment. After 3 years of follow-up, the patient is recovered, with no clinical signs or symptoms of the disease.

Resumo A miíase furuncular é uma infecção parasitária causada pelas larvas de insetos Dipterans após penetrar na pele saudável, causando um nódulo eritematoso contendo um poro central. Adicionalmente, uma sensação de movimento e dor intermitente pode ser sentida. Miíase furuncular acometendo a região oral e perioral é rara, frequentemente causando erros diagnósticos. Este artigo descreve um caso raro de miíase furuncular em um paciente do sexo masculino de 20 anos de idade que apresentou um nódulo eritematoso no lábio inferior. Uma cirurgia exploratória foi indicada para fins diagnósticos e curativos, com sucesso observado já na sessão seguinte. Após 3 anos de acompanhamento, o paciente está recuperado, sem sinais clínicos ou sintomas da doença.

Loss of expression of Plag1 in malignant transformation from pleomorphic adenoma to carcinoma ex pleomorphic adenoma.

PLAG1 (pleomorphic adenoma gene 1) is frequently activated in pleomorphic adenoma (PA). Carcinoma ex pleomorphic adenoma (CXPA) arises in PA, and PLAG1 expression is believed to be maintained from PA to CXPA, as it can contribute to the carcinogenesis process. To evaluate if PLAG1 is a good marker of malignant transformation from PA to CXPA as well as to evaluate if PLAG1 expression is associated with progression and histopathologic subtype of CXPA. Forty PAs, 21 residual PAs (without malignant transformation), and 40 CXPAs were analyzed by immunohistochemistry with PLAG1 antibody. The proportion of positive neoplastic cells was assessed according to a 2-tiered scale: >10% to 50%, and >50% positive cells. The CXPA group was classified according to histopathologic subtype and invasiveness degree. Thirty-seven PAs (92.5%), 15 residual PAs (71%), and 14 CXPAs (35%) were positive for PLAG1. In relation to the CXPA group, among the intracapsular cases, myoepithelial carcinoma and epithelial-myoepithelial carcinoma showed the highest level of PLAG1 expression. PLAG1 expression is lost when PA undergoes malignant transformation, possibly due to other pathway activation and different clone cells. In addition, PLAG1 expression seems to be present mainly in low-grade carcinomas and in cases with early phase of invasion, due to its regulation of oncogene-induced cell senescence. In CXPA, PLAG1 expression was most associated with myoepithelial differentiation. This way, loss of PLAG1 expression can be considered a hallmark of CXPA carcinogenesis, mainly when there is only epithelial differentiation.