Metastasizing pleomorphic adenoma of the parotid gland: A common tumour with a very unusual presentation / Metástasis de adenoma pleomorfo de la glándula parótida: un tumor frecuente con una presentación muy poco habitual

Metastasizing pleomorphic adenoma is recognized as a subtype of pleomorphic adenoma in WHO classification 5th edition of salivary glands. The controversy pertaining to the entity is the benign features of the disease even at a metastatic site. We present a rare case of left recurrent pre-auricular swelling in a young male reported as metastasizing pleomorphic adenoma. A nineteen-year-old male presented with left preauricular swelling seven years ago which was diagnosed as pleomorphic adenoma and underwent complete excision of tumour. The tumour recurred twice – two and five years after the surgery. At the second recurrence, the level II neck dissection showed multiple encapsulated deposits of pleomorphic adenoma having similar morphology in the cervical soft tissue with no features of high-grade transformation. (AU)

La metástasis de adenoma pleomorfo está reconocida como un subtipo de adenoma pleomorfo según la clasificación de tumores de las glándulas salivales de la Organización Mundial de la Salud (OMS), 5ª edición. La controversia sobre la entidad se refiere a las características benignas de la enfermedad, incluso en lugares de metástasis. Presentamos un raro caso, en un varón de 19 años, de inflamación preauricular izquierda recurrente que se comunica como una metástasis de adenoma pleomorfo. El paciente presentó inflamación preauricular izquierda hace siete años, que se diagnosticó como adenoma pleomorfo, y se sometió a una resección completa del tumor, el cual presentó dos recidivas, dos y cinco años después de la cirugía. En la segunda recidiva, la resección a nivel II del cuello mostró múltiples depósitos encapsulados de adenoma pleomorfo de morfología similar en el tejido blando cervical, sin características de transformación de alto grado. (AU)

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.

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.

Prognosticators of Excision of Giant Intra-Oral Tumors in a Resource-Challenged Setting: A Case Report.

Minor salivary glands are widely distributed in the mucosal surface of the lips, palate, nasal cavity, pharynx, and larynx, thus can arise from any of these primary sites. Intra-oral minor salivary gland tumors (IMSGTs), while considered rare in the general population are relatively more common when compared to all the other extra-oral sites. Pleomorphic adenoma, as seen in the index patient, is the most commonly diagnosed benign IMSGT. Intra-oral minor salivary gland tumors are not uncommon and depending on their size, nature, and location can be associated with severe limitation of the Patient's ability to breathe, speak clearly, and/or swallow and consequent severe morbidity and even mortality. In addition to these deleterious effects, they present a major surgical challenge to the surgeon, who has to determine the safest, most feasible access to ensure complete, or near-complete excision, as well as to the anesthetist, who needs to secure a definitive airway through the nose or mouth, both of which could be significantly restricted by the presence of the tumor. The aim is to present our successful management of one of the largest intra-oral minor salivary gland tumors documented in the literature, highlighting the specific measures we undertook to tackle the peculiar surgical and anesthetic challenges we faced. It had been two years since surgery and the patient is thriving with a markedly improved quality of life and no features of recurrence. The patient is a 50-year-old male with a slowly growing painless, left palatal mass in the roof of the mouth of 10 years duration with recurrent spontaneous bloody discharge effluent and snoring. There was an associated history of dysphagia to solid with associated choking spells, a left-sided facial asymmetry with no cheek swelling, odynophagia, sore throat, or difficulty with breathing. There was ipsilateral loss of upper incisors and dental anarchy about two years before presentation. No other nasal, otologic, or ophthalmic symptoms were present. No neck swelling, stiffness, cough, or chest symptoms. The oropharyngeal physical examination was highly restricted due to the intra-oral size of the mass. Figure 1. There was facial asymmetry with a bulge of the left maxilla, left-sided levels 1b and 2 non-tender lymph node enlargements, freely mobile, not adhered to the skin. A craniofacial CT scan revealed extensive isodense heterogeneously enhancing intra-oral soft tissue mass occupying the entire palate/oral cavity and encroaching laterally on the masticator and the parapharyngeal space with erosion of the left maxillary floor and hyoid bone Figure 2. The patient had an excision biopsy of the palatal mass with a free margin. No frozen section at the time of surgery. Histology revealed Pleomorphic adenoma and was followed up for 2 years with no evidence of recurrence. Prognosticators are delay in presentation leading to an increase in size of the mass and severe limitation of the patient's ability to breathe, speak clearly, and/or swallow and consequent severe morbidity and even mortality, the surgeon not being overwhelmed, the skillful Anaesthesist that could maneuver the nasal cavity without us doing tracheostomy and the successful outcome of the surgery.

Les glandes salivaires mineures sont largement réparties à la surface muqueuse des lèvres, du palais, de la cavité nasale, du pharynx et du larynx, et peuvent donc survenir à partir de l'un de ces sites primaires. Les tumeurs des glandes salivaires mineures intra-orales (TGSMIO), bien que considérées comme rares dans la population générale, sont relativement plus courantes par rapport à tous les autres sites extra-oraux. L'adénome pléomorphe, tel que celui observé chez le patient index, est la TGSMIO bénigne la plus fréquemment diagnostiquée. Les tumeurs des glandes salivaires mineures intra-orales ne sont pas rares et, en fonction de leur taille, de leur nature et de leur emplacement, peuvent être associées à une limitation sévère de la capacité du patient à respirer, à parler clairement et/ou à avaler, avec une morbidité sévère et même une mortalité. Outre ces effets délétères, elles présentent un défi chirurgical majeur pour le chirurgien, qui doit déterminer l'accès le plus sûr et le plus faisable pour assurer une excision complète ou presque complète, ainsi que pour l'anesthésiste, qui doit assurer une voie aérienne définitive par le nez ou la bouche, tous deux pouvant être significativement restreints par la présence de la tumeur. L'objectif est de présenter notre prise en charge réussie de l'une des plus grandes TGSMIO documentées dans la littérature, mettant en évidence les mesures spécifiques que nous avons prises pour relever les défis chirurgicaux et anesthésiques particuliers auxquels nous avons été confrontés. Deux ans après l'intervention, le patient se porte bien avec une nette amélioration de sa qualité de vie et aucune manifestation de récurrence. Le patient est un homme de 50 ans présentant une masse palatine gauche en croissance lente et indolore dans le palais depuis 10 ans, avec des écoulements sanguins spontanés récurrents et des ronflements. Il y avait une histoire associée de dysphagie aux solides avec des épisodes d'étouffement, une asymétrie faciale du côté gauche sans tuméfaction de la joue, une odynophagie, un mal de gorge ou des difficultés respiratoires. Il y avait une perte ipsilatérale des incisives supérieures et une anarchie entaire environ deux ans avant la présentation. Aucun autre symptôme nasal, otologique, ophtalmique n'était présent. Aucun gonflement du cou, raideur, toux ou symptômes thoraciques. L'examen physique de l'oropharynx était fortement limité en raison de la taille intra-orale de la masse. Figure 1. Il y avait une asymétrie faciale avec une bosse du maxillaire gauche, des ganglions lymphatiques non douloureux des niveaux 1b et 2 du côté gauche, mobiles librement, non adhérents à la peau. La tomodensitométrie craniofaciale a révélé une masse tissulaire molle intraorale extensive, hétérogène, rehaussée de manière isodense occupant l'ensemble du palais/cavité buccale et empiétant latéralement sur les muscles masticateurs et l'espace parapharyngé, avec érosion du plancher du maxillaire gauche et de l'os hyoïde. Figure 2. Le patient a subi une biopsie d'excision de la masse palatine avec une marge libre. Aucune section congelée n'a été réalisée lors de la chirurgie. L'histologie a révélé un adénome pléomorphe et un suivi de 2 ans n'a montré aucun signe de récurrence. Les facteurs pronostiques comprennent le retard de la présentation entraînant une augmentation de la taille de la masse et une limitation sévère de la capacité du patient à respirer, à parler clairement et/ou à avaler, avec une morbidité sévère voire une mortalité, le chirurgien ne se laissant pas dépasser, l'anesthésiste compétent pouvant manœuvrer dans la cavité nasale sans avoir recours à une trachéotomie, et le succès de l'intervention chirurgicale. MOTS-CLÉS: Intraoral; Glande salivaire mineure; Excision; Tumeur; Pronostiqueurs.

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.

Multispectral optoacoustic tomography of benign parotid tumors in vivo: a prospective observational pilot study.

Parotid lumps are a heterogeneous group of mainly benign but also malignant tumors. Preoperative imaging does not allow a differentiation between tumor types. Multispectral optoacoustic tomography (MSOT) may improve the preoperative diagnostics. In this first prospective pilot trial the ability of MSOT to discriminate between the two most frequent benign parotid tumors, pleomorphic adenoma (PA) and Warthin tumor (WT) as well as to normal parotid tissue was explored. Six wavelengths (700, 730, 760, 800, 850, 900 nm) and the parameters deoxygenated (HbR), oxygenated (HbO2), total hemoglobin (HbT), and saturation of hemoglobin (sO2) were analyzed. Ten patients with PA and fourteen with WT were included (12/12 female/male; median age: 51 years). For PA, the mean values for all measured wave lengths as well as for the hemoglobin parameters were different for the tumors compared to the healthy parotid (all p < 0.05). The mean MSOT parameters were all significantly higher (all p < 0.05) in the WT compared to healthy parotid gland except for HbT and sO2. Comparing both tumors directly, the mean values of MSOT parameters were not different between PA and WT (all p > 0.05). Differences were seen for the maximal MSOT parameters. The maximal tumor values for 900 nm, HbR, HbT, and sO2 were lower in PA than in WT (all p < 0.05). This preliminary MSOT parotid tumor imaging study showed clear differences for PA or WT compared to healthy parotid tissue. Some MSOT characteristics of PA and WT were different but needed to be explored in larger studies.

Oral cavity salivary gland pleomorphic adenoma: a histomorphological case series.

BACKGROUND: Pleomorphic adenoma (PA), the most common benign salivary gland epithelial lesion, has a biphasic epithelial-mesenchymal pattern and great histopathological diversity. METHODS: This study's objective was to conduct a retrospective clinicopathological analysis, focusing on the histopathology characteristics of salivary gland PA. RESULTS: There were ten cases of pleomorphic adenoma. The mean age was 33.5 years and no gender predilection was observed. All the patients presented with an asymptomatic mass and the duration of presentation was 31.2 ± 19.4 months. The cellular subtype (50 %) of PA was the most common. Capsular infiltration and incomplete capsules occurred in 20 % of cases. All the cases had round (100 %) and myxoid stroma. The cellular subtype was more common in the major salivary glands; showed capsular abnormalities (incomplete capsule, absent capsule, and tumor infiltration); and had more plasmacytoid, angular, spindled non-luminal cells as well as inflammation and cystic degeneration. The classic subtype had more clear and oncocytic cells along with sebaceous and squamous differentiation. The stroma-rich subtype had the shortest duration of complaints (three months) and showed giant cell reaction. CONCLUSIONS: These findings confirm previous studies on the clinicopathological features of pleomorphic adenomas and highlight important morphologic characteristics like capsular invasion and squamous metaplasia, which can otherwise indicate malignancy.

[Efficacy analysis of 23 cases of parapharyngeal space tumors removed by oral approach assisted by plasma and high-definition endoscopic system].

Objective:To explore the selection, efficacy and application of indications for parapharyngeal space tumor resection assisted by plasma and HD endoscopic system through oral approach. Methods:The clinical data of 23 patients with parapharyngeal space tumor resection assisted by plasma and HD endoscopic system were retrospectively analyzed in Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hospital of Bengbu Medical University from January 2013 to June 2023. All cases were examined by high-resolution CT and MRI before operation, and some cases were examined by CTA or DSA. During the operation, the high definition nasal endoscopic recording system was assisted, and low temperature plasma knife was used in some cases. The follow-up time was from 3 to 115 months, and the median follow-up time was 45 months. Results:There were no deaths in this group. All patients had complete tumor resection. The maximum tumor diameter was as follows: （5.20±1.00） cm, the operation time was（128.70±46.67） min, and the average blood loss was（80.87±32.74） mL. One case of vascular smooth muscle tumor had more bleeding during the operation and was assisted by tracheotomy after operation. One case of nourishing vascular bleeding after operation of giant Schwannoma was investigated and hemostasis + external carotid artery ligation. Bleeding in the remaining cases was below 120 mL. Postoperative pathologies were all benign tumors, including 11 pleomorphic adenoma, 4 schwannoma, 2 base cell adenoma, 1 epidermoid cyst, 1 lymphatic cyst with infection, 1 angiomyoma, 1 solitary fibroma, 1 salivary gland cyst, and 1 tendon giant cell tumor. All patients were followed up. One patient originating from vagal schwannoma had 2-month vocal cord paralysis and 1 recurrence（recurrence of the skull base of schwannoma）. Conclusion:Oral approach assisted by plasma and high-definition endoscopic system is suitable for partial selective resection of benign tumors in parapharyngeal space, which has the advantages of less trauma and rapid recovery. When the tumor is blood-rich, suspected to be malignant, the top of the tumor is deep into the cranial base nerve canal,located outside the internal carotid artery, and larger than 6.0 cm considering pleomorphic adenoma, it is recommended to conduct an external open or auxiliary cervical small incision approach.

Metastasizing pleomorphic adenoma of the parotid gland: A common tumour with a very unusual presentation.

Metastasizing pleomorphic adenoma is recognized as a subtype of pleomorphic adenoma in WHO classification 5th edition of salivary glands. The controversy pertaining to the entity is the benign features of the disease even at a metastatic site. We present a rare case of left recurrent pre-auricular swelling in a young male reported as metastasizing pleomorphic adenoma. A nineteen-year-old male presented with left preauricular swelling seven years ago which was diagnosed as pleomorphic adenoma and underwent complete excision of tumour. The tumour recurred twice - two and five years after the surgery. At the second recurrence, the level II neck dissection showed multiple encapsulated deposits of pleomorphic adenoma having similar morphology in the cervical soft tissue with no features of high-grade transformation.

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.

Fenestration of the facial nerve by the stylomastoid artery.

BACKGROUND: Anatomic landmarks such as the tympanomastoid suture line, posterior belly of the digastric muscle, tragal pointer, and styloid process can assist the parotid surgeon in identifying and preserving the facial nerve. Vascular structures such as the posterior auricular artery and its branch, the stylomastoid artery, lay in close proximity to the facial nerve and have been proposed as landmarks for the identification of the facial nerve. In this case report, we describe an anatomic variation in which the stylomastoid artery has fenestrated the main trunk of the facial nerve, dividing it in two. METHODS: Two patients underwent parotidectomy (one for a pleomorphic adenoma, the second for a parotid cyst) through a standard anterograde approach with identification of the usual facial nerve landmarks. RESULTS: The appearance of the main trunk of the facial nerve was unusual in both patients due to its being fenestrated by the stylomastoid artery. The stylomastoid artery was divided, and the remainder of the facial nerve dissection was performed uneventfully with subsequent resection of the parotid mass in both patients. CONCLUSIONS: In rare instances, the stylomastoid artery can penetrate through the common trunk of the facial nerve. This is an important anatomic variant for the parotid surgeon to be aware of, as it can increase the difficulty of facial nerve dissection.

Characterization of parotid gland tumors using diffusion-relaxation correlation spectrum imaging: a preliminary study.

AIM: To assess the performance of diffusion-relaxation correlation spectrum imaging (DR-CSI) in the characterization of parotid gland tumors. MATERIALS AND METHODS: Twenty-five pleomorphic adenomas (PA) patients, 9 Warthin's tumors (WT) patients and 7 malignant tumors (MT) patients were prospectively recruited. DR-CSI (7 b-values combined with 5 TEs, totally 35 diffusion-weighted images) was scanned for pre-treatment assessment. Diffusion (D)-T2 signal spectrum summating all voxels were built for each patient, characterized by D-axis with range 0∼5 × 10-3 mm2/s, and T2-axis with range 0∼300ms. With boundaries of 0.5 and 2.5 × 10-3 mm2/s for D, all spectra were divided into three compartments labeled A (low D), B (mediate D) and C (high D). Volume fractions acquired from each compartment (VA, VB, VC) were compared among PA, WT and MT. Diagnostic performance was assessed using receiver operating characteristic analysis and area under the curve (AUC). RESULTS: Each subtype of parotid tumors had their specific D-T2 spectrum. PA showed significantly lower VA (8.85 ± 4.77% vs 20.68 ± 10.85%), higher VB (63.40 ± 8.18% vs 43.05 ± 7.16%), and lower VC (27.75 ± 8.51% vs 36.27 ± 11.09) than WT (all p<0.05). VB showed optimal diagnostic performance (AUC 0.969, sensitivity 92.00%, specificity 100.00%). MT showed significantly higher VA (21.23 ± 12.36%), lower VB (37.09 ± 6.43%), and higher VC (41.68 ± 13.72%) than PA (all p<0.05). Similarly, VB showed optimal diagnostic performance (AUC 0.994, sensitivity 96.00%, specificity 100.00%). No significant difference of VA, VB and VC was found between WT and MT. CONCLUSIONS: DR-CSI might be a promising and non-invasive way for characterizing parotid gland tumors.

[Diagnosis and treatment of subglottic mass（report of 5 cases）].

Subglottic masses is very rare. The clinical data of five cases of subglottic mass in our hospital from 2017 to 2022 were summarized, and their clinical manifestations, auxiliary examination findings, treatment plan and pathological features were analyzed. Among the 5 patients, 1 case was subglottic pleomorphic adenoma, 1 case was subglottic granuloma, 1 case was subglottic breast cancer metastasis, 1 case was subglottic primary adenoid cystic carcinoma, and 1 case was immunoglobulin G4-related disease. No recurrence was observed in the patients so far. Subglottic mass is easy to be missed. Therefore, when the lesion is suspected in this area, the examination of ear, nose and throat should be carried out systematically to detect the lesion early and improve the prognosis.

Proceedings of the 2024 North American Society of Head and Neck Pathology Companion Meeting, Baltimore, MD, March 24, 2024: Navigating Ancillary Studies in Basaloid/Blue Salivary Tumors.

BACKGROUND: Basaloid salivary tumors can demonstrate significant morphologic overlap and be challenging to diagnose. METHODS: A review of select ancillary studies in basaloid salivary tumors was performed. RESULTS: A number of immunohistochemical stains, including PLAG1, HMGA2, ß-catenin, MYB, and RAS Q61R, have been more recently incorporated into the diagnostic workup of basaloid salivary tumors. CONCLUSIONS: Although reported variability in their performance has perhaps limited their widespread adoption, these immunohistochemical studies can nevertheless be useful in supporting pathologic diagnoses, particularly when considered in more specific differentials or when used as a panel with other markers.

Characterization of a Molecularly Distinct Subset of Oncocytic Pleomorphic Adenomas/Myoepitheliomas Harboring Recurrent ZBTB47-AS1::PLAG1 Gene Fusion.

Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal rearrangement is identified in the pleomorphic adenoma gene 1 (PLAG1) gene, different gene partners are found. Oncocytic metaplasia, characterized by oncocytes with abundant eosinophilic granular cytoplasm and hyperchromatic nuclei, is a well-known phenomenon in salivary gland neoplasms. However, the pure oncocytic variant of PA/ME showed PLAG1 gene rearrangements involving various gene partners at the molecular level, without any recurrent fusion being found. Our study includes 20 cases of PA/ME, with 11 females and 9 males. The age of patients ranged from 37 to 96 years, with a median age of 62.8 years. Most tumors originate from the parotid gland. The median size of the tumor was 26.5 mm (range: 13 to 60 mm). Among the 20 cases, 14 were a pure oncocytic variant of PA/ME, whereas 6 cases showed focal oncocytic or oncocytic-like aspects. Molecular studies on 20 cases of PA/ME were conducted. A novel recurrent ZBTB47-AS1::PLAG1 fusion was identified in 6 of 12 cases with pure oncocytic metaplasia, whereas the other cases had PLAG1 gene fusion with different gene partners. The transcriptomic analysis of the cases harboring ZBTB47-AS1::PLAG1 fusion demonstrated that these tumors have a distinct molecular profile from conventional PA/ME. This study reveals a unique subset in the oncocytic PA/ME spectrum characterized by pure oncocytic morphology with larger oncocytic cells and recurrent ZBTB47-AS1::PLAG1 fusion. It also highlights the transcriptomic distinctness of salivary gland adenomas with pure oncocytic metaplasia in the spectrum of salivary gland neoplasms. Further studies are needed to better understand the oncocytic variant of PA/ME and to determine the true nature of oncocytic cells in PA/ME.

Correlation between MRI (DWI and DCE) and cellularity of parotid gland pleomorphic adenomas.

PURPOSE: Parotid pleomorphic adenomas present a risk of recurrence, higher when the tumour is a hypocellular subtype. The aim of the study was to determine whether it is possible to characterize this histological subtype with diffusion and perfusion sequences of the preoperative MRI. METHODS: This retrospective study included 97 patients operated between 2010 and 2020. Histologic slides review was performed to classify tumours into three histologic subtypes: hypocellular, classical and hypercellular. Univariate and multivariate analyses studied the correlation between histology and diffusion and perfusion MRI parameters obtained with OleaSphere® software. RESULTS: The hypocellular subtype had higher apparent diffusion coefficient values than the other two subtypes: 2.13 ± 0.23, 1.83 ± 0.42, and 1.61 ± 0.4 × 10-3 mm2/s for hypocellular, classical and hypercellular subtype respectively (p < 0.0001). Multivariate analysis showed that an ADCmean > 1.88 × 10-3 mm2/s was suggestive of a hypocellular pleomorphic adenoma in 79% of the cases, with a specificity and PPV of 94 and 96% (p < 0.001), respectively. CONCLUSION: The histological subtype of a pleomorphic adenoma can be predicted preoperatively with ADC values. A prospective and multicentric study on a larger cohort is needed to confirm our results.

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

OBJECTIVE: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

EZH2 immunoexpression in pleomorphic adenoma and adenoid cystic carcinoma and clinicopathological features.

The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy.

Spatial insights into immunotherapy response in non-small cell lung cancer (NSCLC) by multiplexed tissue imaging.

The spatial localisation of immune cells within tumours are key to understand the intercellular communications that can dictate clinical outcomes. Here, we demonstrate an analysis pipeline for highly multiplexed CODEX data to phenotype and profile spatial features and interactions in NSCLC patients that subsequently received PD1 axis immunotherapy. We found that regulatory T cells (Tregs) are enriched in non-responding patients and this was consistent with their localization within stromal and peripheral tumour-margins. Proximity-based interactions between Tregs and both monocytes (p = 0.009) and CD8+ T cells (p = 0.009) were more frequently found in non-responding patients, while macrophages were more frequently located in proximity to HLADR+ tumour cells (p = 0.01) within responding patients. Cellular neighbourhoods analysis indicated that both macrophages (p = 0.003) and effector CD4+ T cells (p = 0.01) in mixed tumour neighbourhoods, as well as CD8+ T cells (p = 0.03) in HLADR+ tumour neighbourhoods were associated with favorable clinical response. Evaluation of the inferred regulatory functions between immune cells relative to the tumour suggested that macrophages exhibit an immunosuppressive phenotype against both CD4+ and CD8+ T cells, and that this association scores more highly in ICI refractory patients. These spatial patterns are associated with overall survival in addition to ICI response and may thus indicate features for the functional understanding of the tumour microenvironment.

An ultrasound-based histogram analysis model for prediction of tumour stroma ratio in pleomorphic adenoma of the salivary gland.

OBJECTIVES: Preoperative identification of different stromal subtypes of pleomorphic adenoma (PA) of the salivary gland is crucial for making treatment decisions. We aimed to develop and validate a model based on histogram analysis (HA) of ultrasound (US) images for predicting tumour stroma ratio (TSR) in salivary gland PA. METHODS: A total of 219 PA patients were divided into low-TSR (stroma-low) and high-TSR (stroma-high) groups and enrolled in a training cohort (n = 151) and a validation cohort (n = 68). The least absolute shrinkage and selection operator regression algorithm was used to screen the most optimal clinical, US, and HA features. The selected features were entered into multivariable logistic regression analyses for further selection of independent predictors. Different models, including the nomogram model, the clinic-US (Clin + US) model, and the HA model, were built based on independent predictors using logistic regression. The performance levels of the models were evaluated and validated on the training and validation cohorts. RESULTS: Lesion size, shape, cystic areas, vascularity, HA_mean, and HA_skewness were identified as independent predictors for constructing the nomogram model. The nomogram model incorporating the clinical, US, and HA features achieved areas under the curve of 0.839 and 0.852 in the training and validation cohorts, respectively, demonstrating good predictive performance and calibration. Decision curve analysis and clinical impact curves further confirmed its clinical usefulness. CONCLUSIONS: The nomogram model we developed offers a practical tool for preoperative TSR prediction in PA, potentially enhancing clinical decision-making.