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)

Response to Osilodrostat Therapy in Adrenal Cushing's Syndrome.

Cushing's disease (CD) is the most common cause of endogenous hypercortisolism. Osilodrostat was demonstrated to be efficient in treating CD, and the mean average dose required for CD control was <11 mg/day. Potential differences in osilodrostat treatment between cortisol-producing adenoma (CPA) and CD have not been reported. The aim of this study was to present two patients with CPA in whom significant differences in the response to therapy compared to CD were found. We demonstrated a case of inverse response of cortisol levels with adrenal tumor progression during the initial dose escalation (Case 1). Simultaneously, severe exaggeration of hypercortisolism symptoms and life-threatening hypokalemia occurred. A further rapid dose increase resulted in the first noticeable cortisol response at a dose of 20 mg/day, and a full response at a dose of 45 mg/day. We also present a case that was initially resistant to therapy (Case 2). The doses required to achieve the first response and the full response were the same as those for Case 1. Our study demonstrated that osilodrostat therapy in patients with CPA may require a different approach than that in CD, with higher doses, faster dose escalation, and a possible initial inverse response or lack of response.

Surgical treatment of pituitary neuroendocrine tumors with coexisting intracranial lesions: A case series and review of the literature.

Background: Pituitary neuroendocrine tumors (PitNETs) are a diverse group of benign neoplasms that account for a significant proportion of intracranial tumors (13%). The coexistence of PitNET with other intracranial lesions, such as meningiomas and intracranial aneurysms, has been constantly reported in the literature; yet, the pathophysiological mechanisms remain unknown, and the appropriate management is controversial. This study aims to describe the clinical characteristics, surgical treatment, and outcomes of patients with PitNET with coexisting intracranial lesions in a single healthcare center. Methods: A retrospective analysis was conducted on 12 patients who underwent surgical treatment for PitNET and another intracranial lesion at our single tertiary referral center over 15 years from January 2008 to May 2023. Results: Among these coexisting lesions, aneurysms were the most commonly found (41.67%), followed by meningiomas (33.33%). Surgical intervention for both lesions was performed in a single-stage procedure for most cases (75%), employing transcranial, endoscopic endonasal, and combined approaches. We found low preoperative Karnofsky Performance Scale scores in three patients, with significant differences in functional outcomes. Conclusion: These findings contribute to the limited knowledge about PitNET coexisting with other intracranial lesions and emphasize the importance of patient-tailored, multidisciplinary management in these unusual scenarios.

Imaging features and surgical management of giant parathyroid adenoma with autoinfarction.

Autoinfarction of a parathyroid adenoma can have an atypical clinicoradiologic features that can mimic an inflammatory process or malignancy. In addition, the associated fibrosis makes surgical resection more challenging than for regular parathyroid adenomas. The implications of these findings are that while autoinfarction of parathyroid adenomas is a rare phenomenon, this entity should be considered when there are heterogeneous and cystic components on imaging in patients without hypercalcemia. Ultimately, histopathology is necessary for definitive diagnosis.

A case report of mediastinal parathyroid carcinoma in a chronic kidney disease patient: Addressing management conundrum.

Parathyroid carcinoma is a rare malignancy; and it is rarer to find one located in an ectopic location. Ectopic parathyroid glands are a reported cause of failed primary surgery for hyperparathyroidism. We report here a 73-year-old male who previously had parathyroidectomy for primary hyperparathyroidism but then had recurrence of his symptoms with a diagnosis of a mediastinal parathyroid carcinoma on further evaluation. This presentation of complicated mediastinal parathyroid carcinoma posed significant diagnostic and management challenges due to comorbid stage IV chronic kidney disease (CKD). Secondly, due to the same comorbid condition, a more aggressive calcimimetic regimen could not be undertaken due to the risk of renal dysfunction with potential progression to dialysis status. Thirdly, he was a high-risk surgical candidate due to significant cardiovascular risks. Ideally, open surgical intervention would be recommended but due to the associated risks, he was managed with robotic-assisted thoracoscopic surgery. He subsequently developed hypocalcemia which normalized with supplemental calcium at follow-up.

Myoepithelioma of the Palatal Minor Salivary Gland: A Case Report.

Myoepithelioma is an uncommon benign tumor of the orofacial region arising from the salivary glands. These tumors are composed of specifically myoepithelial cells lacking ductal differentiation and were initially considered as a type of pleomorphic adenoma. Though they commonly arise from the parotid gland, there are a few cases that emerge from the minor salivary glands of the palate and oral cavity. Myoepitheliomas resemble many other tumors arising from the palate including pleomorphic adenoma. This report depicts a case of myoepithelioma of the minor salivary gland of the palate in a 23-year-old patient and the successful management of the lesion.

Small Cell Carcinoma of the Rectum Associated With a Tubulovillous Adenoma: An Atypical Case Presentation.

Small cell carcinoma of the rectum (SCCR) is a rare and aggressive neuroendocrine tumor. Its association with a tubulovillous adenoma is an exceptional occurrence, presenting significant implications for diagnosis and treatment. This case report details a 62-year-old male, undergoing treatment for hepatocellular carcinoma, presented with symptoms of diarrhea. A colonoscopy initially suggested a benign tubulovillous adenoma, but the presence of discordant clinical findings led to further evaluation. The final diagnosis, established post-surgery, was SCCR originating from a tubulovillous adenoma. This case highlights the diagnostic challenges when unusual presentations arise from atypical pathological findings, especially in patients with concurrent malignancies. The management followed standard care protocols, including robotic transanal surgery, despite the patient's ongoing HCC treatment. This case adds to the limited existing literature on SCCR, particularly its rare association with a tubulovillous adenoma. It emphasizes the importance of a multi-disciplinary approach in diagnosing and managing rare entities in colorectal cancer while demonstrating the feasibility of standard care in patients with complex comorbidities.

Neuronavigation in endoscopic skull base surgery and the accuracy of different MRI sequences.

OBJECTIVE: Neuronavigation is common technology used by skull base teams when performing endoscopic endonasal surgery. A common practice of MRI imagining is to obtain 3D isotopic gadolinium enhanced T1W magnetisation prepared rapid gradient echo (MPRAGE) sequences. These are prone to distortion when undertaken on 3 T magnets. The aim of this project is to compare the in vivo accuracy of MRI sequences between current and new high resolution 3D sequences. The goal is to determine if geometric distortion significantly affects neuronavigation accuracy. METHODS: Patients were scanned with a 3D T1 MPRAGE sequence, 3D T1 SPACE sequence and a CT stereotactic localisation. Following general anaesthesia, patients were registered on the Stealth Station (Medtronic, USA) using a side mount emitter for Electromagnetic navigation. A variety of surgically relevant anatomical landmarks in the sagittal and coronal plane were selected with real and virtual data points measured. RESULTS: A total of 10 patients agreed be enrolled in the study with datapoints collected during surgery. The distance between real and virtual datapoints trended to be lower in SPACE sequences compared to MPRAGE. Paired t test did not demonstrate a significant difference. CONCLUSION: We have demonstrated that navigational accuracy is not significantly affected by the type of MRI sequence selected and that current corrective algorithms are sufficient. Navigational accuracy is affected by many factors, with registration error likely playing the most significant role. Further research involving real time imaging such as endoscopic ultrasound may hopefully address this potential error.

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.

Histopathology of growth hormone-secreting pituitary tumors: State of the art and new perspectives.

Somatotroph (GH) adenomas/PitNETs typically arise from adenohypophysis and are biochemically active, leading to acromegaly and gigantism. More rarely, they present with ectopic origin and do not present overt biochemical or clinical features (silent variants). Histopathological examination should consider the clinical and radiological background, and include multiple steps assessing tumor morphology, pituitary transcription factors (PTFs), hormone secretion, proliferation markers, granulation, and somatostatin receptors (STRs), aimed at depicting as better as possible tumor origin (in case of non-functioning and/or metastatic tumor), and clinical behavior, including response to treatment. GH-secreting tumors are part of the Pit-1 family tumors and can secrete GH only (pure somatotrophs) or co-secrete prolactin (mixed tumors; in this case, various histological subtypes have been identified). Each subtype presents unique radiological, biochemical, and clinical characteristic. Therefore, the integration of biochemical, clinical, radiological, and histopathological elements is fundamental for proper diagnosis and management of pituitary adenomas/PitNETs, to be performed in referral Centers. In more recent times, the importance of genetic and epigenetic evaluation in the characterization of pituitary tumors (i.e., early identification of aggressive variants) has been outlined by some large studies, with the intention of improving targeted treatments.

Association between Intracellular Calcium Signaling and Tumor Recurrence in Human Non-Functioning Pituitary Adenomas.

Clinically non-functioning pituitary adenomas (CNFPAs) are the second most frequent sellar tumor among studies on community-dwelling adults. They are characterized by the absence of hormonal hypersecretion syndrome, and patients present with compressive symptoms, such as a headache and visual field defects. Immunohistochemically, most CNFPAs are of gonadotrope differentiation, with only a few of them being truly null cell adenomas. Although these tumors express receptors for one or more hypothalamic releasing hormones, to what extent this has an impact on the biological and clinical behavior of these neoplasms remains to be defined. In this research, we evaluated the basal and hypothalamic secretagogue-stimulated intracellular calcium mobilization in 13 CNFPAs, trying to correlate this response to the phenotypic features of the patients. Our results indicate that the recurrence of a CNFPA correlates positively with cellular responsiveness, as measured by spontaneous intracellular calcium activity and the ability to respond to multiple hypothalamic secretagogues. We conclude that this finding may be a useful tool for predicting the clinicopathologic behavior of CNFPAs, by testing the variation of cellular responsiveness to hypothalamic secretagogues.

GI genius endoscopy module: a clinical profile.

INTRODUCTION: The identification of early-stage colorectal cancers (CRC) and the resection of pre-cancerous neoplastic lesions through colonoscopy allows to decrease both CRC incidence and mortality. However, colonoscopy miss rates up to 26% for adenomas and 9% for advanced adenomas have been reported. In recent years, artificial intelligence (AI) systems have been emerging as easy-to-use tools, potentially lowering the risk of missing lesions. AREAS COVERED: This review paper focuses on GI Genius device (Medtronic Co. Minneapolis, MN, U.S.A.) a computer-assisted tool designed to assist endoscopists during standard white-light colonoscopies in detecting mucosal lesions. EXPERT OPINION: Randomized controlled trials (RCTs) suggest that GI Genius is a safe and effective tool for improving adenoma detection, especially in CRC screening and surveillance colonoscopies. However, its impact seems to be less significant among experienced endoscopists and in real-world clinical scenarios compared to the controlled conditions of RCTs. Furthermore, it appears that GI Genius mainly enhances the detection of non-advanced, small polyps, but does not significantly impact the identification of advanced and difficult-to-detect adenoma. When using GI Genius, no complications were documented. Only a small number of studies reported an increased in withdrawal time or the removal of non-neoplastic lesions.

Gastric polyps: a retrospective cohort analysis of 23,668 endoscopies indicates changing epidemiological and phenotypic characteristics.

Introduction: Growing adoption of endoscopic procedures in clinical practice has gradually increase the detection rate of gastric polypoid lesions. Aim: To identify the epidemiologic characteristics of gastric polyps as well as changes of these parameters during a 15-year period. Material and methods: We reviewed all the upper endoscopies archived in our database reporting a polypoid lesion from 2003 to 2018. Demographic data, indication for endoscopy, morphological characteristics of polyps, histology, and presence of Helicobacter pylori were collected. We compared the abovementioned data between 2 periods: 2003-2010 and 2010-2018. Results: A total of 989 (4.2%) patients from 23,668 reviewed were identified to harbour a polypoid lesion. Mean patient age was 63.2 years, with 58.8% being female. Most polyps (65.2%) were less than 5 mm in diameter and located in the fundus. Hyperplastic polyps (HPs) were the predominant type (28.6%) while fundic gland polyps (FGPs) were found in 24.1% of patients. Adenomas were the least common type (2.7%). Other pathology was identified in 43.3%. Comparison between the 2 periods revealed a rise of FGPs against HPs with a concomitant shift of location from antrum to fundus and an increase in the number of polyps per patient. Conclusions: FGPs and HPs were the most common polyps found in our cohort, with a change of their pattern during the 15 years. It is imperative to acknowledge the distinct characteristics of gastric polyps so as to properly assess the malignant potential that some of them, or their surrounding gastric mucosa, harbour.

Giant Pleomorphic Adenoma of Infratemporal Fossa: A Rare Case Report.

Of all the head and neck tumors, salivary gland tumors account to 3%. Pleomorphic adenomas are one of the most common benign tumors arising from major salivary glands, although it could also develop from minor salivary glands situated at accessory sites like nasal cavity, pharynx, parapharyngeal space, lacrimal glands etc. Tumors of infratemporal fossa are quite unusual, mainly because of its hidden location in retromaxillary region. We report an unusual case of 65 years old male presenting with complaint of progressive left cheek swelling for 4 years. FNAC revealed pleomorphic adenoma of minor salivary gland tumor. Intraoperatively a giant lobulated tumor was seen occupying almost whole space of infratemporal fossa, which was removed in-toto via open approach. Patient was kept on regular follow up with no evidence of recurrence reported till date.

Pituitary Adenoma Prevalence and Characteristics of Omani Patients: A Single Center Experience.

Objectives: To estimate the incidence of pituitary adenomas (PA) in adult Omani patients and describe its epidemiological, clinical, and radiological characteristics. Methods: In this longitudinal, descriptive study, we reviewed the records of all PA patients from January 2015 to January 2020 who presented at the endocrinology facilities at Sultan Qaboos University Hospital, Muscat. Results: The participants comprised of 112 Omani patients with PA. The incidence of PA among all adult patients at Sultan Qaboos University Hospital (inpatient and outpatient) over five years (2015-2020) was 0.23%. The cohort had a mean age of 41.0±15.0 years. Of the 112 patients included in this study, 79 (70.5%) were women. Nearly half (51; 45.5%) of adenomas were prolactinomas while 46 (41.1%) were non-functioning adenomas, and seven (6.3%) were growth hormone-secreting adenomas while six (5.4%) were adrenocorticotropic hormone secreting adenomas. Headache was present in 67 (59.8%) patients, followed by visual field defects (40; 35.7%), galactorrhea (26; 23.2%), and fatigue (19; 17.0%). The majority of women (45/79; 57.0%) presented with menstrual cycle abnormalities. Radiological appearances were nearly equally distributed between micro- and macroadenomas. Most cases (58/112; 52.0%) of PA were treated medically by cabergoline, octreotide, and replacement therapies such as hydrocortisone and thyroxin, 38 (33.9%) were treated surgically (mainly by trans-sphenoidal pituitary resection), and the remaining 10 (8.9%) cases were subjected to radiotherapy. Medical treatment combined with surgery was employed for 15 (13.4%) patients. Conclusions: In our investigation, PA was primarily prevalent among Omani female patients, and the most common subtype of pituitary tumors was prolactinomas. The most common presentation symptom was headaches; most female patients had menstrual irregularities. Medical treatment was the primary approach for the applicable types of PAs, while surgery and radiotherapy were found to be secondary and tertiary treatment options, respectively.

Steroids-producing nodules: a two-layered adrenocortical nodular structure as a precursor lesion of cortisol-producing adenoma.

BACKGROUND: The human adrenal cortex consists of three functionally and structurally distinct layers; zona glomerulosa, zona fasciculata (zF), and zona reticularis (zR), and produces adrenal steroid hormones in a layer-specific manner; aldosterone, cortisol, and adrenal androgens, respectively. Cortisol-producing adenomas (CPAs) occur mostly as a result of somatic mutations associated with the protein kinase A pathway. However, how CPAs develop after adrenocortical cells acquire genetic mutations, remains poorly understood. METHODS: We conducted integrated approaches combining the detailed histopathologic studies with genetic, RNA-sequencing, and spatially resolved transcriptome (SRT) analyses for the adrenal cortices adjacent to human adrenocortical tumours. FINDINGS: Histopathological analysis revealed an adrenocortical nodular structure that exhibits the two-layered zF- and zR-like structure. The nodular structures harbour GNAS somatic mutations, known as a driver mutation of CPAs, and confer cell proliferative and autonomous steroidogenic capacities, which we termed steroids-producing nodules (SPNs). RNA-sequencing coupled with SRT analysis suggests that the expansion of the zF-like structure contributes to the formation of CPAs, whereas the zR-like structure is characterised by a macrophage-mediated immune response. INTERPRETATION: We postulate that CPAs arise from a precursor lesion, SPNs, where two distinct cell populations might contribute differently to adrenocortical tumorigenesis. Our data also provide clues to the molecular mechanisms underlying the layered structures of human adrenocortical tissues. FUNDING: KAKENHI, The Uehara Memorial Foundation, Daiwa Securities Health Foundation, Kaibara Morikazu Medical Science Promotion Foundation, Secom Science and Technology Foundation, ONO Medical Research Foundation, and Japan Foundation for Applied Enzymology.

An ultrasound-based ensemble machine learning model for the preoperative classification of pleomorphic adenoma and Warthin tumor in the parotid gland.

OBJECTIVES: The preoperative classification of pleomorphic adenomas (PMA) and Warthin tumors (WT) in the parotid gland plays an essential role in determining therapeutic strategies. This study aims to develop and validate an ultrasound-based ensemble machine learning (USEML) model, employing nonradiative and noninvasive features to differentiate PMA from WT. METHODS: A total of 203 patients with histologically confirmed PMA or WT who underwent parotidectomy from two centers were enrolled. Clinical factors, ultrasound (US) features, and radiomic features were extracted to develop three types of machine learning model: clinical models, US models, and USEML models. The diagnostic performance of the USEML model, as well as that of physicians based on experience, was evaluated and validated using receiver operating characteristic (ROC) curves in internal and external validation cohorts. DeLong's test was used for comparisons of AUCs. SHAP values were also utilized to explain the classification model. RESULTS: The USEML model achieved the highest AUC of 0.891 (95% CI, 0.774-0.961), surpassing the AUCs of both the US (0.847; 95% CI, 0.720-0.932) and clinical (0.814; 95% CI, 0.682-0.908) models. The USEML model also outperformed physicians in both internal and external validation datasets (both p < 0.05). The sensitivity, specificity, negative predictive value, and positive predictive value of the USEML model and physician experience were 89.3%/75.0%, 87.5%/54.2%, 87.5%/65.6%, and 89.3%/65.0%, respectively. CONCLUSIONS: The USEML model, incorporating clinical factors, ultrasound factors, and radiomic features, demonstrated efficient performance in distinguishing PMA from WT in the parotid gland. CLINICAL RELEVANCE STATEMENT: This study developed a machine learning model for preoperative diagnosis of pleomorphic adenoma and Warthin tumor in the parotid gland based on clinical, ultrasound, and radiomic features. Furthermore, it outperformed physicians in an external validation dataset, indicating its potential for clinical application. KEY POINTS: • Differentiating pleomorphic adenoma (PMA) and Warthin tumor (WT) affects management decisions and is currently done by invasive biopsy. • Integration of US-radiomic, clinical, and ultrasound findings in a machine learning model results in improved diagnostic accuracy. • The ultrasound-based ensemble machine learning (USEML) model consistently outperforms physicians, suggesting its potential applicability in clinical settings.

Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect.

Cardiac glycosides, known as inhibitors of Na+,K+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.