Pitfalls in Diagnosis of Myoepithelial Carcinoma of Salivary Glands: A Study of 3 Cases with Cytologic-histologic Correlation and Molecular Analysis.

CONTEXT: Myoepithelial carcinoma (MECA) represents < 1% percent of salivary gland (SG) tumors with a mean age of 55 years. These tumors can arise de novo or in association with pre-existing pleomorphic Adenoma (PA). The cytologic features of MECA overlap with other SG neoplasms including the more common benign entities like PA and myoepithelioma and can pose a diagnostic challenge. DESIGN: A database search for MECA was performed spanning 10 years. 3 cases qualified with available cyto-histologic correlation. All were morphologically MECA with one case diagnosed as MECA ex-PA. The cases were subjected to a comprehensive immunohistochemical and molecular evaluation (Case#1 has been previously reported and published in head and neck pathology in 2021). RESULTS: A comparative analysis of these cases is presented in Table 1. All three cases were initially diagnosed as PA on cytology. On review of cytology slides, presence of metachromatic stromal fragments and bland myoepithelial cells was found to be the most common diagnostic pitfall. S100 was positive in all cases while myosin, p63, and GFAP were variably positive. Molecular analysis revealed novel, previously undescribed mutations in the three cases. Additionally, two of three cases expressed PD-L1, suggesting a role for immunotherapy in treatment. CONCLUSIONS: Cytomorphology of MECA is poorly described in literature and can pose a diagnostic challenge due to overlapping features with salivary gland benign neoplasms. A conclusive diagnosis on cytology is often not possible. However, a high cellularity, predominant oncocytoid/ myoepithelial cell population on smears and cell block, along with a strong clinical and radiologic suspicion for malignant salivary gland tumor, should alert the cytopathologist and help avoid an erroneous benign diagnosis on cytology.

Pleomorphic Parotid Adenoma in a Child Affected with Cri du Chat Syndrome: Clinical, Cytogenetic, and Molecular Analysis.

Salivary gland pleomorphic adenoma (SGPA) is the most common type of benign epithelial tumor; it is observed more commonly in females (with a female-to-male ratio of 1.43:1), and the age at diagnosis ranges between 40 and 59 years, with only 2% of cases diagnosed before age 18. Cri du Chat (CdC) is a rare syndrome caused by deletions of various sizes in the short arm of chromosome 5. Tumors in CdC patients are extremely rare: in Danish, Spanish, Australian, and Japanese groups of cases, no tumors have been reported, while a few cases have been described among 321 CdC patients collected in Italy and Germany. These cases all involve tumors that appear at a young age. We here report the case of a parotid pleomorphic adenoma in an 8-year-old boy with CdC. Exome analysis did not identify variants certainly significant for the development of SGPA. A CGH array, analyzed both in peripheral blood and tumor samples, failed to recognize anomalies previously associated with SGPA but identified a de novo duplication in 7p15.2, which contains part of a gene, SKAP2, in which the increased copy number is associated with the development of a different type of tumor such as pancreatic duct adenocarcinoma. The assumption that the duplication in 7p15.2 is relevant for the development of SGPA in our patient implies that CGH array studies must be included early in life in routine work-ups of CdC to identify CNVs with possible pathogenic roles for tumor development. This is particularly also relevant in relation to the severely impaired possibility for patients with CdC to report discomfort or pain related to tumor development. Constitutional CNVs in addition to the deletion in 5p should also be extensively studied to verify if their presence in some patients could explain why, in these cases, tumors develop at an age younger than expected.

Pleomorphic adenoma of hard palate: Review of updated literature and "case report".

RATIONAL: Pleomorphic adenoma (PA) is a rare benign tumor mainly affecting the major salivary glands, known for its diverse histological appearances that can mimic malignancies. When it occurs in the hard palate it present diagnostic and management challenges compared to other sites due to the anatomical location and potential proximity to critical structures. This case reports a rare presentation PA starting as an ulcer, alongside a review of rare cases of PA reported in last 5 years. We aim to highlight clinical challenges and emphasize the need for awareness in diagnosis of this diverse entity amongst the clinicians before reaching a definitive conclusion. PATIENT CONCERNS: A 41-year-old female reported an asymptomatic large swelling on the right side of the posterior palatal region. Clinical diagnosis revealed a firm, rubbery, and non-tender swelling of approximately 4 cm × 4 cm diameter. A triangular incisional biopsy was performed to confirm the diagnosis. DIAGNOSIS: The histopathological evaluation confirmed the presence of a PA with a well-encapsulated and compressed salivary gland. A wide surgical dissection was made to remove the entire encapsulated tumor mass, including the mucoperiosteum and eroded bone of the palate. The borderline of the tumor was carefully identified in the surrounding healthy tissue. The hemostasis was obtained using a simple interrupted suture. LESSON: The diagnosis of PA is difficult as it usually involves extensive squamous and mucous metaplasia, confusing it with malignant disorders. Histopathological and clinical examinations are important for differentiating this lesion from other tumors. Complete surgical excision is reported as the first line of treatment.

Carcinoma ex-pleomorphic adenoma of parotid gland presenting as a gigantic cervicofacial mass.

When neglected for a long time, salivary gland pleomorphic adenoma (PA) can attain a considerable size, increasing the patient's morbidity along with the risk of malignant transformation. Very few case reports are available describing PA of the parotid glands presenting as a large cervicofacial mass. We report a case of epithelial myoepithelial carcinoma -a rare subtype of carcinoma ex-PA (Ca-Ex-PA) of non-luminal differentiation, that developed over a long period in a primary PA of the parotid gland and presented as a giant cervicofacial mass.

Case Series: Pleomorphic adenoma in minor salivary gland.

Pleomorphic adenomas (PA) are the most prevalent benign salivary gland neoplasms. They may occur at any age, with a peak incidence between 40 and 60 years of age. They are more commonly observed in females (60%). These tumors can arise in both the major and minor salivary glands. Approximately 80% of these tumors are diagnosed in the parotid gland, whereas 10% arise in the minor salivary glands, mainly affecting the palates, followed by the lips and cheeks. This report describes two cases of unusual lesions that were diagnosed as (PA) in the minor salivary glands in our department via a review of the relevant literature. The first case involved an 83-year-old man who presented with a slow-growing swelling on the right side of the upper lip, and the second case involved a 45-year-old woman who presented with a slow-growing lesion on the palate. The presence of PA was confirmed histopathologically after surgical resection. Although relatively rare, PA is a benign lesion, the diagnosis of which must be known for appropriate therapeutic management.

Presumed Lacrimal Gland Pleomorphic Adenoma With Extensive Ossification and Necrosis.

Calcification within pleomorphic adenomas of the lacrimal gland is well recognized but uncommon, being seen more readily in lacrimal gland carcinomas. Bony formation, ossification, in pleomorphic adenomas of the lacrimal glands is even rarer. Together with extensive sclerosis, or "coagulative necrosis," ossification and necrosis should alert the clinician to the risk of malignant transformation. However, both can mimic carcinomatous change, leading to misinterpretation of malignancy in an otherwise benign lacrimal gland neoplasm. We present 2 case reports of patients with clinically presumed pleomorphic adenomas of the lacrimal gland whose histopathology demonstrated lacrimal gland ossification and necrosis without features of malignancy or invasive disease.

Acinic cell Carcinoma with high-grade Squamoglandular and Chondrosarcomatous Transformation Mimicking 'Carcinosarcoma ex-pleomorphic Adenoma': A Wrinkle in the Proposed Nomenclature Revision for Sarcomatoid Salivary Gland Neoplasms.

While acinic cell carcinoma (AciCC) can undergo high-grade transformation (HGT) to high-grade adenocarcinoma or poorly differentiated carcinoma, other morphologies such as spindle cell/sarcomatoid carcinoma are rare and not well-characterized. We herein report a novel case of AciCC with squamoglandular and chondrosarcomatous HGT mimicking a so-called 'carcinosarcoma ex-pleomorphic adenoma'. The patient is an 81-year-old male with a two-month history of neck swelling and referred otalgia who presented with a left parapharyngeal space mass extending into retropharyngeal space and pterygoid muscles. On resection, the tumor showed considerable morphologic diversity with high-grade serous and mucous acinar components as well as cribriform to solid apocrine-like components with comedonecrosis and squamous differentiation, all of which were embedded in a chondromyxoid background ranging from paucicellular and bland to a high-grade chondrosarcoma/pleomorphic sarcoma-like appearance. Only a minor conventional AciCC component was noted. Immunostains were negative for AR and only focally positive for GCDFP-15 arguing against a true apocrine phenotype, while PLAG1 and HMGA2 were negative arguing against an antecedent pleomorphic adenoma. On the other hand, SOX-10, DOG-1 and PAS after diastase highlighted serous acinar differentiation, and mucicarmine, and NKX3.1 highlighted mucous acinar differentiation. NR4A3 immunohistochemical staining and NR4A3 fluorescence in situ hybridization were positive in the carcinomatous and sarcomatoid components while sequencing analysis of both components revealed identical alterations involving TP53, PIK3CB, ARID1A, and STK11. This unique case warrants caution in designating all salivary sarcomatoid carcinomas with heterologous elements as part of the 'carcinoma ex-pleomorphic adenoma' family.

Central Pleomorphic Adenoma of Mandible Mimicking Ameloblastoma - A Rare Case Report.

Salivary gland neoplasms account for 3% of all head and neck tumours. Pleomorphic adenoma (PA) is the most common salivary gland tumour that mainly occurs in the parotid gland, followed by minor salivary glands of the oral cavity, however, the occurrence of PA inside the jaw bones is exceedingly rare and very few cases have been reported in the literature. Inside jaw bones these lesions tend to imitate large osteolytic lesions encompass a diagnostic challenge. An exhaustive review of the literature revealed only 10 cases of central pleomorphic adenoma. We present a rare case of primary PA that occurred inside the mandible and was provisionally diagnosed as ameloblastoma.

Case of eccrine chondroid syringoma of the upper lip.

Chondroid syringoma (CS) is a benign, slow-growing mixed tumour that arises from the sweat glands and usually presents in the head and neck area. Histopathological examination is important for proper diagnosis, as CS is often confused with epidermal cysts due to its rare presentation. This article presents a man in his 40s with a right upper lip mass that emerged 6 months prior to presentation. An intraoral surgical excision was performed and the histopathological analysis revealed solid epithelial cells that formed multiple, non-branching ducts lined by cuboidal epithelium. Cystic spaces were filled by heterogeneous eosinophilic material embedded in chondromyxoid stroma. Histopathology identified the lesion as an eccrine-variant CS. The patient recovered well.

Clinical behavior of recurrent pleomorphic adenoma in the palate: a systematic review.

PURPOSE: This systematic review analyzed the clinical behavior and odds of malignancy of the palatal recurrent pleomorphic adenomas. METHODS: Systematic review of patients with recurrent pleomorphic adenoma arising in the palate. Database search: MEDLINE, Scopus, Web of Science, Cochrane, EMBASE, Virtual Health Library, Google Scholar, and OpenGrey. A binomial logistic regression was performed to assess the odds of detecting recurrence five, 10 and 20 years after the treatment of primary tumor. RESULTS: Thirteen studies (n = 18 patients) out of 336 were included. The recurrent pleomorphic adenoma in palate was more common in females (61.6%), average age was 49 years old (range 9-73 years old). Four patients progressed to malignant transformation. The odds ratio (OR) of detecting a recurrence at 10 (OR = 5.57; 95% confidence interval - 95%CI 1.13-27.52), and 20 years (OR = 18.78; 95%CI 3.18-110.84) after treatment of primary pleomorphic adenoma was significantly higher than at one-year follow-up. CONCLUSIONS: The recurrence of pleomorphic adenoma in palate remains a rare event of late occurrence. It mainly affects middle-aged female and carries a risk of malignant transformation. Although uncommon, patients with palatal pleomorphic adenoma should be warned about the possibility of recurrence or malignant transformation of tumor at advanced ages.

Pleomorphic adenoma with extensive squamous and mucinous metaplasia and a novel MALAT1::PLAG1 fusion gene.

Cases of metaplastic pleomorphic adenoma can be diagnostically challenging. Many of these cases fall into the Milan system's SUMP category, and some may be misdiagnosed. The author shows a case of pleomorphic adenoma with extensive squamous and mucinous metaplasia and a novel MALAT1::PLAG1 fusion.

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

OBJECTIVE: 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. DATA SOURCES: MEDLINE, CINAHL, Embase, Scopus, Web of Science (BIOSIS), Cochrane CENTRAL, Health Collection (Informit), OpenDOAR, and GreyNet International. REVIEW METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A Large Pleomorphic Adenoma in Nasal Cavity Misdiagnosed as Inverted Papilloma.

Pleomorphic adenoma (PA) is a benign tumor characterized by slow-growing mixed tumors in the craniofacial area. It is relatively common in salivary glands; however, PA of the nasal cavity, which arises in the minor salivary glands, is rare. We present the case of a large PA in the nasal cavity of an adult immunocompetent woman with nasal obstruction and intermittent epistaxis. Based on preoperative radiologic examinations, she was misdiagnosed with an inverted papilloma. Endoscopic resection was performed under general anesthesia. Pathologically, the patient was confirmed to have PA, which has great cellularity and few stromal components. No complications or recurrences during the 1-year follow-up period were observed.

Chondroid Syringoma on the Tip of the Nose: A Case Report.

ABSTRACT: Chondroid syringoma is a benign, rare, asymptomatic, slow-growing mixed tumor. The authors present the case of a 17-year-old adolescent boy who had a tumor on the tip of his nose for a duration of 8 months. An excisional biopsy was performed under local anesthesia. Based on histopathologic analysis, the resected lesion was identified as a chondroid syringoma.

Analysis of clinical features of 7 cases of primary pleomorphic adenoma of lower respiratory tract and review of literature.

To investigate the clinical characteristics of patients with primary pleomorphic adenoma of the lower respiratory tract. The clinical manifestations, laboratory results, pathological and imaging, treatment and prognosis of 7 patients with primary pleomorphic adenoma of the lower respiratory tract who were treated in Hunan Provincial People's Hospital from December 2015 to May 2020 were analyzed. Among the 7 patients, 5 patients had cough and expectoration as the main clinical manifestations, and the other 2 patients had no symptoms. Pleomorphic adenomas of the lower respiratory tract are mostly located in the trachea or bronchus, and the chest computed tomography findings are circular or ellipsoid masses, or flake high-density shadows and local thickening of the tracheobronchial wall. Tumor histological features and immunohistochemistry can diagnose pleomorphic adenoma and its origin. In this study, 2 asymptomatic patients refused further treatment, 1 survived for more than 3 years, and the other was lost to follow-up during follow-up. One patient with surgical resection was followed up for 5 years after surgery and had a good survival status. The other 4 patients with respiratory symptoms who could not undergo surgery were mainly treated with bronchoscopic interventional therapy on demand, and the survival time up to now was 2 to 5 years. Primary pleomorphic adenoma of the lower respiratory tract is rare in clinic. Its clinical symptoms are related to the location and size of the tumor. Both surgical resection and bronchoscopic intervention have a good clinical prognosis. The cause of death of patients with such diseases is mostly dyspnea caused by tumors in the airway. Early diagnosis, timely intervention and regular follow-up can make patients obtain better curative effect.

Hyaline cell-rich chondroid syringoma: A potential pitfall on cytology.

Chondroid syringoma is a rare adnexal tumor of skin, with few cases diagnosed on fine needle aspiration cytology (FNAC). Hyaline cell-rich chondroid syringoma (HCRCS) is a very uncommon variant of chondroid syringoma described in histopathologic studies. This variant differs from the usual chondroid syringoma in its site of presentation, cytohistologic features, and morphologically mimics malignant neoplasms. To the best of our knowledge, cytologic features of this entity have never been described. This case report highlights some unusual features of this tumor and discusses the cytologic features of HCRCS along with neoplastic mimics.

Basal cell adenoma and pleomorphic adenoma of the parotid gland: a single center experience.

BACKGROUND: Basal cell adenoma (BCA) and pleomorphic adenoma (PA) are among the most common benign neoplasms of the salivary glands. The aim of this study was to analyze and compare the diagnosis, treatment, and recurrence rate of these two different types of parotid benign tumors. METHODS: A retrospective analysis of all cases of parotid gland BCA and PA surgically treated between January 1, 1990, and December 31, 2019, was performed at our university. RESULTS: A total of 349 patients were enrolled in the present study, 311 of which (89.1%) were affected by PA, and 38 patients (10.9%) by BCA. The most frequently performed surgery was partial parotidectomy for both groups (85.9% in PA and 65.8% in BCA). Perioperative complications - often transient and of short duration - occurred within 48 hours of surgery and were observed in 30.6% of PA patients and in 18.4% of BCA patients; furthermore, recurrences were noticed in 19 PA patients (6.2%) and in 3 BCA patients (7.9%) (rates in range with the available literature data). CONCLUSIONS: To the best of our knowledge, this study is one of the largest single-center series in the literature comparing diagnosis, treatment, recurrence rate and clinical-pathological features of two different types of benign parotid gland tumors, BCA, and PA.

Clinicopathological characteristics of pleomorphic adenoma from the labial gland: A 20-year experience with 173 cases in one single institution.

OBJECTIVE: Pleomorphic adenoma (PA) of the lip is not a common phenomenon, and existing literature provides limited information on the clinicopathological features of labial PA. STUDY DESIGN: Patients diagnosed with labial PA at our single institution over the past 20 years (2001-2020) was retrospectively screened and analyzed to investigate the epidemiologic and clinicopathological features of these tumors. RESULTS: A total of 173 cases were screened out, and the average age was 44.3 (range 7-82) years, with a peak incidence rate during the third decade. A slight predilection for men (52%) was observed, and PA occurs more frequently in the upper lip than in the lower lip, with a ratio of 14.7:1. On clinical examination, labial PAs usually present as painless masses that develop slowly with no systemic symptoms. Histologically, labial PAs contain myoepithelial and polygonal epithelial cells in myxoid, hyaline, fibrous, chondroid, and even osseous tissues, similar to those in other sites. Specifically, 15 of 173 patients with labial PA presented with cutaneous PA. CONCLUSION: Labial PA presents over a wide age range and dominantly occurs at the upper lip. Surgical resection is the major treatment strategy, and postoperative recurrence or malignant transformation of labial PA was extremely rare.

Cytopathology of salivary gland myoepithelial carcinoma: A study of 13 cases and review of the literature.

INTRODUCTION: Myoepithelial carcinoma (MECA) is an infrequently recognized salivary gland (SG) neoplasm that commonly develops within a preexisting pleomorphic adenoma (MECA ex PA). Fine-needle aspiration (FNA) biopsy reports of this neoplasm are largely restricted to small series and single case reports. METHODS: Our cytopathology files were searched for examples of SG MECA/MECA ex PA having confirmatory histopathologic verification. Conventional FNA biopsy smears were performed, and exfoliative specimens processed using standard techniques. RESULTS: Thirteen cases from 9 patients (M:F = 3.5:1; age range: 36 to 95 years, mean age = 60 years) met inclusion criteria. FNA biopsy sites included parotid gland (4), trunk (2), scalp (2), and neck (2). Exfoliative specimens included pleural fluid (1), bronchial brushing (1), and bronchoalveolar lavage (1). Most cases were metastatic deposits (8; 62%), 4 were primary neoplasms, and 1 a local recurrence. FNA diagnoses were MECA ex PA (6; 46%), myoepithelial neoplasm (2), PA (2), basaloid neoplasm (1), atypical myoepithelial cells (1), and myxoma (1). Ancillary testing in 2 cases showed positive staining for myoepithelial markers. Cytologic features were that of a low-grade neoplasm composed principally of epithelioid/polygonal cells exhibiting minimal if any cytologic atypia. Myxoid and chondromyxoid stroma was often the dominant feature in MECA ex PA aspirates. CONCLUSION: In the primary setting, a cytologic diagnosis of MECA/MECA ex PA is extremely challenging if at all possible. Due to overwhelming amounts of stroma, the diagnosis may be challenging in some cases of metastatic MECA ex PA.

Updated Salivary Gland Immunohistochemistry: A Review.

CONTEXT.­: Salivary gland neoplasms are rare lesions in the head and neck (H&N) pathology realm. There are more than 20 malignant and 15 benign salivary gland neoplasms in the 5th edition of the World Health Organization classification of H&N tumors. These neoplasms consist of heterogeneous groups of uncommon diseases that make diagnosis and treatment challenging for the clinical team. Using an algorithmic immunohistochemical approach-defined tumor origin and type has proven to be effective and advantageous. Immunohistochemistry may be used as sort of a "diagnostic looking glass," not as a positive or negative type tool, but as an indispensable complement to a hematoxylin-eosin morphologic pattern-based approach. Furthermore, the understanding of the novel discoveries of the salivary gland gene fusions and the molecular aspects of these tumors makes the process easier and improve the diagnosis as well as treatment aspects. This review reflects our experience with more recent diagnostic antibodies, which include MYB RNA, Pan-TRK, PLAG1, LEF1, and NR4A3. Each of these is linked with a specific type of neoplasm; for example, gene fusions involving the PLAG1 and HMGA2 oncogenes are specific for benign pleomorphic adenomas, and MYB is associated with adenoid cystic carcinoma. OBJECTIVE.­: To review these more recent antibodies, which highly enhance salivary gland neoplasm diagnosis. DATA SOURCES.­: The study sources involved literature PubMed searches, including multiple review articles, case reports, selected book chapters, and Geisinger Medical Center cases. CONCLUSIONS.­: Salivary gland tumors are a rare, varied group of lesions in H&N pathology. We need to have continuous readings and revisions of the molecular consequences of these fusion oncoproteins and their subsequent targets, which will eventually lead to the identification of novel driver genes in salivary gland neoplasms.