Management of Multiple Head and Neck Paragangliomas With Assistance of a 3-D Model

Introduction: Extirpation of multiple head and neck paragangliomas carries challenge due to close anatomic relationships with critical neurovascular bundles. Objectives: This study aims to assess whether the application of 3-D models can assist with surgical planning and treatment of these paragangliomas, decrease surgically related morbidity and mortality. Methods: Fourteen patients undergoing surgical resection of multiple head and neck paragangliomas were enrolled in this study. A preoperative 3-D model was created based on radiologic data, and relevant critical anatomic relationships were preoperatively assessed and intraoperatively validated. Results: All 14 patients presented with multiple head and neck paragangliomas, including bilateral carotid body tumors (CBT, n = 9), concurrent CBT with glomus jugulare tumors (GJT, n = 4), and multiple vagal paragangliomas (n = 1). Ten patients underwent genomic analysis and all harbored succinate dehydrogenase complex subunit D (SDHD) mutations. Under guidance of the 3-D model, the internal carotid artery (ICA) was circumferentially encased by tumor on 5 of the operated sides, in 4 (80%) of which the tumor was successfully dissected out from the ICA, whereas ICA reconstruction was required on one side (20%). Following removal of CBT, anterior rerouting of the facial nerve was avoided in 3 (75%) of 4 patients during the extirpation of GJT with assistance of a 3-D model. Two patients developed permanent postoperative vocal cord paralysis. There was no vessel rupture or mortality in this study cohort. Conclusion: The 3-D model is beneficial for establishment of a preoperative strategy, as well as planning and guiding the intraoperative procedure for resection of multiple head and neck paragangliomas.

The emerging clinical relevance of genomic profiling in neuroendocrine tumours

Background Neuroendocrine tumours (NETs) arise from hormone-producing or nervous system cells and can develop from anywhere in the body. They have heterogeneous origins from skin to gastrointestinal track and a complicated histology. Thus, there is an inevitable need for genomic profiling to determine the exact genetics of each tumour for prognosis and treatment strategies to overcome the disease’s complexity. For this purpose, next-generation-sequencing (NGS) is the most reliable methodology for both germ-line and somatic studies to make a clinical diagnosis. In this study, we analyse liquid biopsies, formalin fixed paraffin embedded (FFPE) tissues, and peripheral blood samples for their ability to provide information for actionability. Methods A customized multi-gene panel comprised of Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB), Succinate Dehydrogenase Complex Subunit C (SDHC), Cell Division Cycle 73(CDC73), Calcium Sensing Receptor (CASR), Platelet Derived Growth Factor Receptor Alpha (PDGFRA), Succinate Dehydrogenase Complex Flavoprotein Subunit A (SDHA), Ret Proto-Oncogene (RET), Succinate Dehydrogenase Complex Assembly Factor 2(SDHAF2), Menin 1(MEN1), Succinate Dehydrogenase Complex Subunit D (SDHD), MYC Associated Factor X (MAX) and Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha (PRKAR1A) genes was constructed to assess multiple specimen types including: 3 liquid biopsies, 6 FFPE tissues, and 26 peripheral blood samples from 35 unique NET patients. Quality-control and bioinformatics analyses were performed using QCI-Analyze and QCI-Interpret. Results The three liquid biopsies and the 6 FFPE tissue samples were evaluated for somatic mutations; while the 26 peripheral blood samples were analysed using the germ-line pipeline. Five (55.6%) of the nine patients that were studied for somatic changes carried actionable mutations related to therapy sensitivities. Through the germ-line studies, we observed a 50% positivity rate for disease predisposition with 16 variants classified according to ACMG (American College of Medical Genetics) Standards and Guidelines. Conclusions Genomic profiling medicine is an emerging area of clinical oncology and has become crucial for disease and patient management by providing a precision approach; this is especially true for rare diseases including rare cancers such as NETs. Notably, this study emphasized the relevance of multiple distinctive biological sample types for use in the genetic testing of cancers to help with the choice of therapy to maximize the likelihood of a positive clinical outcome.

Regional metastatic paraganglioma of the bladder: a rare cause of myocardial infarction, reversible cardiomyopathy and an intracardiac thrombus

Sympathetic paragangliomas are rare neuroendocrine tumours that arise from chromaffin cells and secrete catecholamines. On rare occasions, patients with sympathetic paragangliomas can present with symptoms of congestive heart failure. The optimal treatment is surgical to remove all disease and thereby improve survival as well as restore cardiac function. We report a case of a patient with a regional metastatic bladder paraganglioma and a succinate dehydrogenase complex subunit B gene mutation presenting with cardiomyopathy who had significant improvement in his cardiac function with surgical resection despite further progression of metastatic disease. During his 4-year follow-up period, the patient remains free from heart-failure signs and symptoms.

Quantitative Analysis of CCL5 and ep300 in Periapical Inflammatory Lesions

<p><strong>Objectives. </strong><em>In silico </em>bioinformatical analysis suggested that the expression of two genes, <em>CCL5 </em>(C-C Motif Chemokine Receptor 5) and <em>ep300 </em>(Histone acetyltransferase p300), could be used as potential new biomarkers in differentiation between periapical granulomas and radicular cysts. Thus, we hypothesized that gene expression of <em>CCL5 </em>and <em>ep300 </em>in periapical lesions would classify the lesions as either granuloma or cyst.</p><p><strong>Materials. </strong>Patient samples (n=122) included 46 periapical granulomas, 38 radicular cysts and 38 healthy gingival samples as controls. Real-time PCR analysis of <em>CCL5 </em>and <em>ep300 </em>transcripts was compared to <em>SDHA </em>(Succinate dehydrogenase complex, subunit A) as the reference. Clinical parameters (e.g., intensity of inflammation and lesion size) were measured and correlated with <em>CCL5 </em>and <em>ep300 </em>expression. ROC (Receiver operating characteristic) and logistic regression analyses were used to establish the diagnostic character of ΔCt values.</p><p><strong>Results. </strong>Granulomas and radicular cysts had significantly higher expression of <em>CCL5 </em>and <em>ep300 </em>compared to controls (P&lt;0.05). However, no differences were observed when comparing granulomas and radicular cysts. ROC analyses showed that <em>CCL5 </em>and <em>ep300 </em>have good diagnostic accuracy, but low accuracy for distinguishing between the lesions.</p><p><strong>Conclusions. </strong>This study confirmed that expression of <em>CCL5 </em>and <em>ep300 </em>is relevant for the pathogenesis of periapical inflammatory lesions but cannot be used as a distinctive marker between these lesions.</p>

A rare case of familial middle mediastinal paraganglioma

A 57-year-old lady with a history of familial paraganglioma syndrome type 4 with mutation in the succinate dehydrogenase complex, subunit B gene, had a nonfunctioning middle mediastinal paraganglioma. She also had a pituitary macroadenoma with elevated serum prolactin levels. Surgical excision of the highly vascular mediastinal tumor was performed after preparing the patient preoperatively with alpha blockers and strictly monitoring her blood pressure and blood sugar levels.

Thyroid Paraganglioma

Thyroid paragangliomas are rare tumors that arise from the inferior laryngeal paraganglia. Most patients are female and present with an asymptomatic thyroid nodule. Histologically, the tumor is composed of cells arranged in a well-defined nest (zellballen) pattern surrounded by a thin fibrovascular stroma. It is a diagnostic pitfall and is occasionally misdiagnosed as follicular neoplasm, medullary thyroid carcinoma, intrathyroid parathyroid proliferation, and especially secondary neuroendocrine tumors. Immunohistochemical stains (cytokeratin, parathyroid hormone, thyroid transcription factor 1, tyrosine hydroxylase, chromogranin A, synaptophysin, S100, calcitonin, carcinoembryonic antigen) are essential in establishing the diagnosis. Loss of succinate dehydrogenase complex, subunit B (SDHB), immunoexpression can be used to triage genetic testing because some mutations are associated with a higher risk for developing metastasis. Total thyroidectomy or lobectomy for solitary lesion is the preferred treatment. Elective lymph node dissection is usually not indicated. Postoperatively, patients should receive hormonal evaluation for functional disease and imaging for evaluation of multifocal or metastatic disease.