Carcinoma Ex Pleomorphic Adenoma Research Articles

Peculiar nuclear atypia associated with MDM2 gene amplification in carcinoma ex-pleomorphic adenoma harbouring an alteration of HMGA2.

Salivary gland neoplasms (SGN) exhibiting the HMGA2::WIF1 fusion are recognized by their resemblance to histology found in canalicular adenoma. Recently, ~20% of cases among 28 HMGA2::WIF1-rearranged-SGN showed malignancy and adverse outcomes (recurrence, distant metastasis, and disease-specific mortality). Among them, MDM2/CDK4 amplifications were identified in one case. This outcome suggests that the MDM2/CDK4 amplifications could be useful to predict an aggressive course of carcinoma ex-pleomorphic adenoma (CEPA). We investigated the correlation between HMGA2 fusion and MDM2 amplification in four salivary gland neoplasms, providing detailed clinicopathological features and outcomes. Cases were selected from different institutions. Histological examination, immunohistochemistry, fluorescence insitu hybridization (FISH), RNA sequencing, and whole-exome capture were performed. The cohort included four CEPA cases, all female, aged between 32 and 89 years. Tumours arose from the parotid gland with an average size of 24.5 mm. None exhibited recurrence or distant metastases during the 4-5 months of follow-up. Pathologically, all cases displayed a peculiar atypical nuclei with 'gear-like appearance'. Immunohistochemically, tumours exhibited a biphasic pattern with myoepithelial and ductal differentiation markers. All cases showed HMGA2 overexpression and MDM2 amplification by FISH and RNA sequencing. In a control cohort of MDM2 nonamplified CEPA cases, not exhibiting the peculiar nuclear atypia. Our findings suggest a strong correlation between HMGA2 alteration/MDM2 amplification and a peculiar nuclear atypia, advocating for their evaluation in biphasic tumours to facilitate accurate diagnosis and tailored posttumour removal monitoring. Further studies are warranted to validate these observations and elucidate their prognostic implications.

Dendritic cell subpopulations in carcinoma ex-pleomorphic adenoma: A multicenter study.

Carcinoma ex-pleomorphic adenoma (CEXPA) represents a malignant transformation from a recurrent or primary pleomorphic adenoma (PA), and the immune response may be essential in this process. Therefore, in this study, we aimed to identify and quantify subpopulations of dendritic cells (DCs) in CEXPA, residual PA in CEXPA (rPA), and PA. A multicenter study was performed collecting salivary gland tumor (SGT) samples from three Oral and Maxillofacial Pathology Centers. A tissue microarray containing 41 samples of CEXPA and 22 samples of PA was included in this study and submitted to immunohistochemical reactions against CD1a, CD83, CD207, and Ki67 antibodies. Both PA and rPA showed a higher quantification of CD207+ and CD83+ cells when compared to CEXPA (p < 0.001 and p < 0.01, respectively). There was also a difference when comparing the cell proliferation index between PA/rPA and CEXPA using the Ki-67 marker (p = 0.043). However, there was no difference in the DC population regarding clinical parameters such as sex, anatomical location, size, and metastases (p > 0.06). Immunohistochemical profile of DC subpopulations and cell proliferation biomarkers in SGTs can contribute as an important tool in the differentiation of benign and malignant tumors or detection of initial areas with malignant transformation.

A 22-year single institution review of 119 cases of salivary duct carcinoma.

Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date. This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed. This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease (p<.001), distant metastasis (p<.001), perineural invasion (p = .027), and lymphovascular invasion (p = .018) were predictive of decreased OS and DSS. Trastuzumab administration was not associated with survival in HER-2-positive patients receiving chemotherapy. Multivariate analyses demonstrated that presence of nodal disease (HR 30.337, 95% CI 2.782-330.851, p = .005) and carcinoma ex pleomorphic adenoma (HR 5.54, 95% CI 1.024-29.933, p = .047) were associated with decreased OS. Our patients had more favorable survival rates compared to prior studies, which may be due to lower incidence of nodal disease. Factors associated with worse survival included nodal and distant metastases, perineural invasion, lymphovascular invasion, and tumor size. Level 3.

MicroRNA copy number alterations in the malignant transformation of pleomorphic adenoma to carcinoma ex pleomorphic adenoma.

This study used array comparative genomic hybridization to assess copy number alterations (CNAs) involving miRNA genes in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA), residual PA, and carcinoma ex pleomorphic adenoma (CXPA). We analyzed 13 PA, 4 RPA, 29 CXPA, and 14 residual PA using Nexus Copy Number Discovery software. The miRNAs genes affected by CNAs were evaluated based on their expression patterns and subjected to pathway enrichment analysis. Across the groups, we found 216 CNAs affecting 2261 miRNA genes, with 117 in PA, 59 in RPA, 846 in residual PA, and 2555 in CXPA. The chromosome 8 showed higher involvement in altered miRNAs in PAs and CXPA patients. Six miRNA genes were shared among all groups. Additionally, miR-21, miR-455-3p, miR-140, miR-320a, miR-383, miR-598, and miR-486 were prominent CNAs found and is implicated in carcinogenesis of several malignant tumors. These miRNAs regulate critical signaling pathways such as aerobic glycolysis, fatty acid biosynthesis, and cancer-related pathways. This study was the first to explore CNAs in miRNA-encoding genes in the PA-CXPA sequence. The findings suggest the involvement of numerous miRNA genes in CXPA development and progression by regulating oncogenic signaling pathways.

Never too young for a salivary gland carcinoma ex-pleomorphic adenoma

BackgroundCarcinoma ex-pleomorphic adenoma (CXPA) can either arise primarily as a de novo or from the malignant transformation of a benign pleomorphic adenoma (PA). CXPA mostly occurs in adults aged 50 to 70 years; hence, the occurrence of CXPA in younger ages is not common.Case presentationWe report a 27-year-old female who had a history of submandibulectomy for pleomorphic adenoma, and presented with recurrent left submandibular swelling for 4 months. The mass was rapidly increasing in size and was associated with occasional throbbing pain. Examination showed a multilobulated, firm left submandibular swelling with no overlying skin changes. FNAC was performed twice, by conventional and ultrasound-guided techniques, and both concluded as benign salivary gland tumours. CT scan and MRI revealed a well-demarcated tumour with an area of necrosis within, with no obvious invasion into surrounding soft tissue and no significant lymphadenopathy. Having high suspicion of a malignant transformation, the tumour was resected with a concurrent modified radical neck dissection. The histopathological examination confirmed a carcinoma ex-pleomorphic adenoma with the myoepithelial malignant component. The patient subsequently received adjuvant radiotherapy. This case demonstrated that CXPA, although rare, can occur in young adults. Pre-operative FNAC and radiological imaging may mimic a pleomorphic adenoma.ConclusionThe presence of recurrent tumours with rapid growth should alarm the clinician about a possible malignant transformation of a benign parotid tumour.

Carcinoma Ex Pleomorphic Adenoma - Report of a Rare Case in the Cheek Mucosa

Carcinoma ex pleomorphic adenoma (CEPA) is a malignization of pleomorphic adenoma and often evolves silently. Its occurrence is rare and predominantly affects the major salivary glands, with the palate being the most common intraoral location. It is recognized as a condition with difficult clinical and pathological diagnosis, and histopathology remains the gold standard for definitive diagnosis. This study presents a primary CEPA in the buccal mucosa identified in a 69-year-old female patient. Less invasive tumors are associated with good prognosis; therefore, early recognition is important as they can become more aggressive, leading to more comprehensive therapies and reserved prognoses.

Influence of p16 Protein Immunostaining on Histopathological Features of Pleomorphic Adenoma and Carcinoma ex- Pleomorphic Adenoma.

The objective of this study was to evaluate the role of p16 in histologic characteristics and transition of Pleomorphic Adenoma (PA) to Carcinoma ex-PA (CxPA). So, 60 PA and 4 CxPA were histologic reviewed based on microscopic characteristics proposed by Hellquist, Triantafyllou and Dulguerov (PA) and Morais, Antony and Toluie (CxPA). Immunostaining for p16 was associated in different parenchyma and stroma of both tumors and Fisher's/chi-square tests and Mann-Whitney test were performed (SPSS v20.0, p<0.05). In PA the periductal cells were predominantly p16- and that ductal and myoepithelial cells showed a significant increase in p16+ cells (p<0.001). In CxPA, none of the cases showed p16+ in periductal cells, most parotid cases showed p16+ in ductal cells, and one case of parotid and the submandibular case showed mild immunostaining for myoepithelial cells. There was a small reduction in p16+ in CxPA compared to PA (p=0.537), but in both tumors there was less p16+ cells in solid stroma than other (p<0.001). The p16+ cases of PA had a higher capsular thickness (p=0.047). So, the loss of p16 immunostaining does not seem to be associated with the transition from PA to CxPA, but in both tumors the loss of p16+ cells are related to microscopic aggressiveness.

Clinicopathological characteristics of four major histological types of high-grade parotid carcinoma.

High-grade parotid carcinoma generally has a poor prognosis, and the histological type is mucoepidermoid carcinoma (MEC), salivary duct carcinoma (SDC), carcinoma ex pleomorphic adenoma (CEPA), or adenoid cystic carcinoma (AdCC) in the majority of cases. During the 23-year period from September 1999 to December 2022, 250 patients with parotid carcinoma underwent initial treatment and had the histopathological type of their carcinoma. Retrospective study evaluated 111 MEC, SDC, CEPA, or AdCC cases among 134 patients with high-grade parotid carcinoma. We examined pathological and clinical features and prognosis, evaluated factors associated with recurrence, and performed immunohistological examinations. Pathological and clinical features and factors associated with recurrence were different for each histological type. The 10-year disease-free survival rates were as follows: MEC, 34.9%; SDC, 22.6%; CEPA, 47.1%; and AdCC, 56.3%. Human epidermal growth factor receptor type-2 and androgen receptor were positive in 48% and 56% of patients with SDC, respectively, 38% and 25% of those with CEPA. Each histological type has its own pathological and clinical features, recurrence types, and tumor activities, suggesting that differentiating between high-grade parotid carcinomas according to histological type will improve diagnosis, and thus prognosis.

Risk of Carcinoma in Pleomorphic Adenomas of the Parotid

Surgery is the mainstay of treatment for pleomorphic adenomas (PAs) of the parotid to prevent further growth and potential future malignant transformation. While historical case series have reported transformation rates as high as 10%, there is a lack of contemporary methodologically sound data. To examine the rate of carcinoma ex pleomorphic adenoma (CXPA) detection in untreated PAs and investigate factors associated with malignant neoplasm. This cohort study reviewed all cases of primary PAs managed at a quaternary referral center between December 1990 and January 2015. Patients whose clinical presentation was compatible with a primary benign PA and whose history indicated tumor duration of over 1 year were included. Data were analyzed from January to April 2023. Untreated PA. Rate of CXPA detection among untreated PAs and association of tumor duration with rates of CXPA detection. Pathology slides of patients who underwent surgery were reviewed by a single expert pathologist for the presence of CXPA. Univariable logistic regression was performed to evaluate possible factors associated with CXPA. A total of 260 patients (median age, 47 years [IQR, 38-60 years]; 174 [66.9%] female) had a median tumor duration of 3.2 years (range, 1-30 years; mean [SD], 5.7 [5.5] years). Patients were divided into 4 groups by tumor duration: 1 to 4 years (158 [60.7%]), 5 to 9 years (47 [18.1%]), 10 to 14 years (27 [10.4%]), and 15 to 30 years (28 [10.8%]). In 156 of 170 patients who underwent preoperative fine-needle aspiration (91.8%), a benign tumor was diagnosed; 5 of these patients (3.2%; 95% CI, 1.4%-7.3%) were later diagnosed with CXPA on pathology after eventual excision, and the rate of high grade CXPA was 1.3%. None of the patients had permanent facial nerve paralysis. Tumor size at presentation (odds ratio [OR], 1.66; 95% CI, 1.22-2.24) and incremental (per year) increase in age (OR, 1.04; 95% CI, 1.01-1.08) were found to be associated with CXPA, whereas tumor duration was not (OR, 1.00; 95% CI, 1.00-1.01). In this study, the rate of malignant neoplasm detection among initially untreated PA was 3.2%. The results suggest that tumor size and older age are associated with the development of CXPA, while tumor duration is not. Observation of PA for longer periods was not associated with serious permanent complications.

Don't SUMP it! Utility of PLAG1 immunocytochemistry in basaloid SUMP subcategory.

Basaloid salivary gland neoplasm of uncertain malignant potential (B-SUMP) is an indeterminate diagnostic subcategory, with pleomorphic adenoma (PA) representing the most common benign neoplasm. Pleomorphic adenoma gene 1 (PLAG1) staining is frequently seen in PAs and could aid in distinguishing them from other basaloid neoplasms. The authors evaluated the utility of PLAG1 immunocytochemistry (ICC) in differentiating PAs from other basaloid neoplasms in smears and liquid-based cytology (LBC) specimens. In total, 45 B-SUMP cytology aspirates and corresponding surgical excision specimens were identified. PLAG1 immunostaining was performed in all aspirates and surgical excision specimens and was scored as positive (strong/diffuse), equivocal (focal/weak), or negative. PLAG1 ICC was performed directly on 38 smears and seven LBC specimens. PLAG1 was positive in 29 of 45 cases (64%), whereas six of 45 (13%) were equivocal, and 10 of 45 (22%) were negative. PLAG1-positive aspirates included 26 (90%) PAs, two (7%) basal cell adenomas (BCAs), and one (3%) carcinoma ex-PA. PLAG1-equivocal aspirates included four (67%) PAs and two (33%) BCAs, whereas negative aspirates included five (50%) BCAs, four (40%) adenoid cystic carcinomas, and one (10%) metastatic adenosquamous carcinoma. The sensitivity, specificity, positive, and negative predictive values were 87%, 86%, 93%, and 75%, respectively. Diagnostic accuracy was 87%. PLAG1 ICC is useful when positive (strong/diffuse) and can be reliably performed on smears and LBC specimens. PLAG1 was positive in most PAs and in a small subset of BCAs. Therefore, in the absence of atypical cytologic features, PLAG1-positive tumors could be diagnosed as benign, with a note favoring PA versus BCA. In contrast, PLAG1-negative/equivocal tumors should remain in the B-SUMP category.

Metastasis of solitary fibrous tumor to the parotid gland diagnosed on aspiration cytology supplemented with immunocytochemistry.

Solitary fibrous tumor (SFT) can occur in varied anatomic locations, most commonly being the extremities-superficial and deep soft tissues, followed by retroperitoneum, visceral organs, and the bone. Head and neck region may harbor a few with a predilection for the orbit and sinonasal tract, oral cavity, and rarely the salivary glands. The parotid gland is most involved among all salivary glands. Overall, SFT in salivary glands is rare and mostly seen as a primary tumor. The occurrence of metastasis to the parotid gland is exceedingly uncommon. We present cytological findings of SFT, metastatic to the parotid gland in a young 31-year-old lady where the diagnosis was confirmed with the help of immunocytochemistry (ICC) on the cell block. The smears were highly cellular and showed predominantly discrete round to oval tumor cells with mild pleomorphism, coarse chromatin, inconspicuous nucleoli, and scanty cytoplasm. Mitosis and focal areas of necrosis were noted. Lymphoglandular bodies were absent ruling out a non-Hodgkin lymphoma. Features were of a poorly differentiated malignant tumor with differentials being sarcoma, myoepithelial carcinoma, and carcinoma ex-pleomorphic adenoma. A panel of ICC was done and positivity for signal transducer and activator of transcription 6 (STAT6) helped in clinching the correct diagnosis of SFT.

Molecular Factors in Carcinoma Ex Pleomorphic Adenoma: Systematic Review and Meta-Analysis.

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor. Although multiple reviews have been published on salivary gland malignancies, it has been a decade since the last dedicated systematic review pertaining to CXPA alone was published. This study examines molecular factors in CXPA diagnosis. MEDLINE, CINAHL, Embase, Scopus, Web of Science (BIOSIS), Cochrane CENTRAL, Health Collection (Informit), OpenDOAR, and GreyNet International. Systematic review and meta-analysis from inception to October 31, 2022 for all English language studies pertaining to "carcinoma ex pleomorphic adenoma." Predicted incidence of each biomarker was calculated with meta-analysis. Comparison against pleomorphic adenoma (PA) and salivary duct carcinoma (SDC) when reported within the same study are performed. Risk of bias performed with JBI tool for prevalence studies. Of 19151 unique studies undergoing abstract screening, 55 studies (n = 1322 patients) underwent data analysis. Biomarkers with >3 studies were p53, HER2, AR, EGFR, PLAG1, ERBB, ER, PR, HMGA2, p16, p63, a-SMA, RAS, PTEN, PDL1, BRAF, PIK3CA, and c-kit. Highest incidence was seen in AR, EGFR, p16, and p53. Significant differences were demonstrated compared with PA and SDC. There was high heterogeneity and overall high risk of bias within studies. Molecular factors are an area of interest in the diagnosis of CXPA. Our study results support examining CXPA as a discrete cohort in future targeted therapy trials. Laryngoscope, 134:1042-1053, 2024.

Loss of BAP1 Protein Expression by Immunohistochemistry in the Salivary Duct Carcinoma Component of an Intracapsular Carcinoma ex Pleomorphic Adenoma of the Parotid Gland.

BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is altered in a variety of neoplasms as well as in BAP1 tumor predisposition syndrome. BAP1 alterations are associated with aggressive behavior in some malignancies and may have treatment implications in future. We present the first documented case of loss of BAP1 protein expression by immunohistochemistry in the salivary duct carcinoma (SDC) component of an intracapsular carcinoma ex pleomorphic adenoma (CXPA) in the context of molecular loss of function of BAP1 in the neoplasm. A woman of approximately 55years of age presented with a deep parotid lobe mass, which was resected and found to be CXPA. BAP1 immunohistochemistry and next-generation sequencing was performed to further characterize the neoplasm. The neoplasm showed loss of BAP1 protein expression in the SDC component but retention in the residual pleomorphic adenoma (PA). Next-generation sequencing confirmed a BAP1 loss of function alteration in the neoplasm. This is the first documented case report of BAP1 protein expression loss in the SDC component of a CXPA. Future studies are needed to investigate the relevance of BAP1 alterations in SDC and CXPA, which may have prognostic and treatment implications.

Evaluation of Fine Needle Aspiration Cytopathology in Salivary Gland Tumors under Milan System: Challenges, Misdiagnosis Rates, and Clinical Recommendations.

(1) Background: Salivary gland tumors are rare in the head and neck. To determine the need and extent of surgical intervention, fine needle aspiration (FNA) is a widely accepted tool to approach salivary gland lesions. However, the FNA cytology varies between entities, while the lack of uniform terminology makes diagnosis more challenging. Since establishing the Milan system for reporting salivary gland cytopathology (MSRSGC) has become an increasingly accepted reporting standard, further examination and detailed recommendations were needed. (2) Methods: Between April 2013 and October 2021, 375 cases with FNA and salivary gland resection were retrospectively collected. All FNA specimens were reclassified according to the criteria of MSRSGC. After surgical excision, the FNA data were compared with the histological diagnosis to estimate the risk of malignancy (ROM), the risk of neoplasm (RON), and the diagnostic accuracy for each diagnostic category. (3) Results: Our cohort's distribution of ROM and RON was similar to the MSRSGC's recommendation. Carcinoma ex pleomorphic adenoma (CXPA) has the highest rate (66.7%) of misdiagnosed as a nonneoplastic lesion or benign salivary gland tumor. Pleomorphic adenoma (PA) and Warthin's tumor were the most common benign salivary gland tumors, while the cytology diagnosis of Warthin's tumor seems more challenging than PAs. (4) Conclusions: Despite the convenience and effectiveness of MSRSGC, we suggest close follow-up, re-biopsy, or surgical removal for salivary lesions even in Milan IVA-Benign for possibly missing FNA of malignancy, mixed lesions, or prevention of malignant transformation.

Extracellular matrix remodelling and stiffening contributes to tumorigenesis of salivary carcinoma ex pleomorphic adenoma——A study based on patient-derived organoids

BackgroundSalivary carcinoma ex pleomorphic adenoma (CXPA) is defined as a carcinoma that develops from benign pleomorphic adenoma (PA). Abnormally activated Androgen signaling pathway and amplification of HER-2/neu(ERBB-2) gene are known to be involved in CXPA tumorigenesis. Recent progress in tumour microenvironment research has led to identification that extracellular matrix (ECM) remodelling and increased stiffness act as critical contributing role in tumour carcinogenesis. This study examined ECM modifications to elucidate the mechanism underlying CXPA tumorigenesis.ResultsPA and CXPA organoids were successfully established. Histological observation, immunohistochemistry (IHC), and whole-exome sequencing demonstrated that organoids recapitulated phenotypic and molecular characteristics of their parental tumours. RNA-sequencing and bioinformatic analysis of organoids showed that differentially expressed genes are highly enriched in ECM-associated terms, implying that ECM alternations may be involved in carcinogenesis. Microscopical examination for surgical samples revealed that excessive hyalinized tissues were deposited in tumour during CXPA tumorigenesis. Transmission electron microscopy confirmed that these hyalinized tissues were tumour ECM in nature. Subsequently, examination by picrosirius red staining, liquid chromatography with tandem mass spectrometry, and cross-linking analysis indicated that tumour ECM was predominantly composed of type I collagen fibers, with dense collagen alignment and an increased level of collagen cross-linking. IHC revealed the overexpression of COL1A1 protein and collagen-synthesis-related genes, DCN and IGFBP5 (p < 0.05). Higher stiffness of CXPA than PA was demonstrated by atomic force microscopy and elastic imaging analysis. We utilized hydrogels to mimic ECM with varying stiffness degrees in vitro. Compared with softer matrices (5Kpa), CXPA cell line and PA primary cells exhibited more proliferative and invasive phenotypes in stiffer matrices (50Kpa, p < 0.01). Protein-protein interaction (PPI) analysis of RNA-sequencing data revealed that AR and ERBB-2 expression was associated with TWIST1. Moreover, surgical specimens demonstrated a higher TWIST1 expression in CXPA over PA. After knocking down TWIST1 in CXPA cells, cell proliferation, migration, and invasiveness were significantly inhibited (p < 0.01).ConclusionDeveloping CXPA organoids provides a useful model for cancer biology research and drug screening. ECM remodelling, attributed to overproduction of collagen, alternation of collagen alignment, and increased cross-linking, leads to increased ECM stiffness. ECM modification is an important contributor in CXPA tumorigenesis.

Comparative impact of grade on mortality across salivary cancers: A novel, unifying staging system.

The comparative impact of histologic variants and grade has not been well described. Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival. On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73). Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.

CARCINOMA EX-PLEOMORPHIC ADENOMA IN A YOUNG PATIENT WITH AN UNUSUAL FAMILY HISTORY

This study aimed to report a case of a young woman (21 years old) complaining of an oral lesion for approximately 5 years. The patient reported an unusual family history, with a brother who died at age of 20 with multiple myelomas. During physical examination, a tumor was found on the hard palate, measuring 8 × 5 cm, covered by an erythematous mucosa with telangiectasia, and with a fibrous consistency. Radiographic examination revealed no signs of bone erosion. Incisional biopsy confirmed pleomorphic adenoma. Just fifteen days after the procedure, patient returned with an exophytic ulcer on the central part of the mass, covered by a necrotic area. A second biopsy was performed, now with the diagnosis of a carcinoma ex-pleomorphic adenoma. The patient underwent follow-up with partial maxillectomy and rehabilitation with bucomaxilofacial prosthesis. After two years of follow-up, the patient presented no signs of recurrence and a good general health. This study aimed to report a case of a young woman (21 years old) complaining of an oral lesion for approximately 5 years. The patient reported an unusual family history, with a brother who died at age of 20 with multiple myelomas. During physical examination, a tumor was found on the hard palate, measuring 8 × 5 cm, covered by an erythematous mucosa with telangiectasia, and with a fibrous consistency. Radiographic examination revealed no signs of bone erosion. Incisional biopsy confirmed pleomorphic adenoma. Just fifteen days after the procedure, patient returned with an exophytic ulcer on the central part of the mass, covered by a necrotic area. A second biopsy was performed, now with the diagnosis of a carcinoma ex-pleomorphic adenoma. The patient underwent follow-up with partial maxillectomy and rehabilitation with bucomaxilofacial prosthesis. After two years of follow-up, the patient presented no signs of recurrence and a good general health.

Frequent apocrine changes in pleomorphic adenoma with malignant transformation: a possible pre-malignant step in ductal carcinoma ex pleomorphic adenoma.

The most common type of carcinoma ex pleomorphic adenoma (CPA) is histologically equivalent to salivary duct carcinoma, which has an apocrine phenotype. Invasive CPA is often accompanied by non-invasive or in situ carcinoma, an observation that suggests the presence of precursor lesions. The aim of this study was to identify candidate precursor lesions of CPA within pleomorphic adenoma (PA). Eleven resected cases of CPA with residual PA and 17 cases of PA with atypical changes were subjected to immunohistochemistry (IHC) for p53, human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), pleomorphic adenoma gene 1, gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody. Invasive or in situ carcinoma cells in all CPAs were positive for AR, GCDFP-15, and HER2. Atypical foci in PAs corresponded to either apocrine or oncocytic changes on the basis of their reactivity to AR, GCDFP-15, and anti-mitochondrial antibody. Atypical cells in PAs surrounding CPAs had an apocrine phenotype without HER2 expression. Our study identified frequent apocrine changes in residual PAs in CPA cases, suggesting a possible precursor role of apocrine changes. We recommend the use of HER2 IHC in atypical PAs, and that clinicians take HER2 positivity into serious consideration.

Heterogeneity and versatility of the extracellular matrix during the transition from pleomorphic adenoma to carcinoma ex pleomorphic adenoma: cumulative findings from basic research and new insights.

Pleomorphic adenoma (PA) is the most common salivary gland tumor, accounting for 50%-60% of these neoplasms. If untreated, 6.2% of PA may undergo malignant transformation to carcinoma ex-pleomorphic adenoma (CXPA). CXPA is a rare and aggressive malignant tumor, whose prevalence represents approximately 3%-6% of all salivary gland tumors. Although the pathogenesis of the PA-CXPA transition remains unclear, CXPA development requires the participation of cellular components and the tumor microenvironment for its progression. The extracellular matrix (ECM) comprises a heterogeneous and versatile network of macromolecules synthesized and secreted by embryonic cells. In the PA-CXPA sequence, ECM is formed by a variety of components including collagen, elastin, fibronectin, laminins, glycosaminoglycans, proteoglycans, and other glycoproteins, mainly secreted by epithelial cells, myoepithelial cells, cancer-associated fibroblasts, immune cells, and endothelial cells. Like in other tumors including breast cancer, ECM changes play an important role in the PA-CXPA sequence. This review summarizes what is currently known about the role of ECM during CXPA development.

Carcinoma Ex Pleomorphic Adenomas: An Institutional Experience and Literature Review.

To provide an institutional experience with cases diagnosed as carcinoma ex pleomorphic adenoma (CXPA), including the cytologic and histologic findings and clinical follow-up, followed by a comparison to the experience documented in the literature. We identified cases of CXPA diagnosed at our institution from 2011 to 2021 and reviewed the cytologic and histologic diagnoses, as well as the treatment and clinical outcomes. Additionally, a literature review of the English literature was performed on CXPAs from 2011 to 2021. Forty-one cases of CXPA were identified, with the majority subclassified as adenocarcinoma, not otherwise specified. Five tumors underwent cytogenetic studies and five underwent molecular studies. To date, 36 patients are alive, 8 of whom experienced locoregional recurrence or distant metastasis. Our institutional experience was comparable to that reported in the literature. Further studies are required to inquire about the role of molecular profiles of CXPAs in clinical risk assessment.