Search Results (6)

Pheochromocytomas and paragangliomas (PPGLs) are infrequent neuroendocrine hypervascular neoplasms arising within different sites of the paraganglion system. They are divided into sympathetic (including pheochromocytomas and extraadrenal paragangliomas) and parasympathetic extraadrenal tumors. These tumors are usually not malignant and grow slowly; about 90% of them are found in the adrenal paraganglia (pheochromocytomas). Extraadrenal tumors are most frequently located in the abdominal cavity (85%), followed by the thoracic cavity (12%), and head and neck (3%). About 25% of PPGLs are related to germline mutations, which are risk factors for multifocal and metastatic disease. In PPGL diagnostics, laboratory, biochemical, and imaging (anatomical and functional) examinations are used. Surgery is the standard management choice for locoregional disease. For patients who are not candidates for surgery and who have stable, not-growing, or slow-growing tumors, active observation or other less invasive techniques (i.e., stereotactic surgery, hypofractionated stereotactic radiotherapy) are considered. In metastatic disease, systemic therapies (tyrosine kinase inhibitors [TKIs], mTORC1 inhibitor everolimus, immunotherapy, cold somatostatin analogs [biotherapy], and radioligand therapy) are used. The prognosis for PPGLs is quite good, and the 5-year survival rate is >90%. The goal of this paper is to review knowledge on the etiopathogenesis, current diagnostics, and therapy for PPGL patients. Our paper is particularly focused on the current management of PPGLs. Full article

(1) Background: Head and neck paragangliomas are neuroendocrine tumors that typically originate from the parasympathetic nervous system and are predominantly non-secretory. Their clinical manifestations result from their mass effect on the surrounding tissues. The approach to treating these tumors depends on factors such as their location, size, impact on adjacent structures, and the patient’s overall health and preferences. (2) Methods: A retrospective analysis of the management of temporal bone paraganglioma classes A and B (according to the modified Fisch classification) was performed at the University Medical Centre, Ljubljana, between 2011 and 2023. (3) Results: We analyzed 23 cases, 19 of which underwent surgery; complete tumor removal was achieved in 18 of them. Four patients were irradiated due to tumor progression to class C. Three of these four patients initially refused surgery and were treated with radiotherapy (RT) 7, 13, and 18 years after diagnosis. In the fourth patient, complete surgical resection was not achieved and she was treated with RT four years after surgery, due to the growth of the tumor to class C. The average follow-up time from diagnosis was 8.9 years (median 6 years; range 1–26 years). (4) Conclusions: The surgical treatment of patients with class A and B paragangliomas is effective and safe. In cases where surgery is refused but the tumor continues to grow to class C, RT is an alternative and efficient method of controlling tumor growth. Full article

Malignant middle ear paraganglioma (MEPGL) is an exceedingly rare tumor of the neuroendocrine system. In general, MEPGLs represent as slow growing and hypervascularized benign neoplasms. The genetic basis of MEPGL tumorigenesis has been poorly investigated. We report a case of malignant MEPGL accompanied by the comprehensive genetic analysis of the primary tumor and metastasis. Based on whole-exome sequencing data, the germline pathogenic mutation p.R230H in the SDHB gene, encoding for subunit B of mitochondrial complex II, was found in a patient. Analysis of somatic mutation spectra revealed five novel variants in different genes, including a potentially deleterious variant in UNC13C that was common for the tumor and metastasis. Identified somatic variants clustered into SBS1 and SBS5 mutational signatures. Of note, the primary tumor was characterized by Ki-67 4% and had an elevated mutational load (1.4/Mb); the metastasis’ mutational load was about 4.5 times higher (6.4/Mb). In addition, we revealed somatic loss of the wild-type SDHB allele, as well as loss of heterozygosity (LOH) at the 11p locus. Thus, germline mutation in SDHB combined with somatic LOH seem to be drivers that lead to the tumor’s initiation and progression. Other somatic changes identified can be additional disease-causing factors. Obtained results expand our understanding of molecular genetic mechanisms associated with the development of this rare tumor. Full article

We describe the case of a 74-year-old female patient previously treated with radiation therapy for a meningioma of the skull base and with surgery for a right tympanic paraganglioma. After the morphological progression of the meningioma demonstrated by magnetic resonance imaging (MRI), the patient underwent somatostatin receptor positron emission tomography/computed tomography (SR-PET/CT) with Gallium-68 DOTATATE for restaging. This examination showed increased somatostatin receptor expression by the meningioma and confirmed its extension as already assessed by MRI (endocranial extension, skull base involvement and invasion of the right orbit). Furthermore, SR-PET/CT detected two small right jugulotympanic pararagangliomas with high somatostatin receptor expression. Lastly, SR-PET/CT demonstrated that this patient would be an ideal candidate for peptide receptor radionuclide therapy (PRRT) that can be used for the treatment of progressive/treatment-refractory meningiomas and relapsed paragangliomas with high somatostatin receptors expression, both conditions coexisting in this case. Full article

Paragangliomas are neuroendocrine neoplasms, derived from paraganglia of the sympathetic and parasympathetic nervous systems. They are most commonly identified in the head and neck, being most frequent in the carotid body, followed by jugulotympanic paraganglia, vagal nerve and ganglion nodosum, as well as laryngeal paraganglia. Abdominal sites include the well-known urinary bladder tumors that originate in the Organ of Zuckerkandl. However, other unusual sites of origin include peri-adrenal, para-aortic, inter-aortocaval, and paracaval retroperitoneal sites, as well as tumors in organs where they may not be expected in the differential diagnosis of neuroendocrine neoplasms, such as thyroid, parathyroid, pituitary, gut, pancreas, liver, mesentery, lung, heart and mediastinum. The distinction of these lesions from epithelial neuroendocrine neoplasms is critical for several reasons. Firstly, the determination of clinical and biochemical features is different from that used for epithelial neuroendocrine tumors. Secondly, the genetic implications are different, since paragangliomas/pheochromocytomas have the highest rate of germline susceptibility at almost 40%. Finally, the characterization of metastatic disease is unique in these highly syndromic lesions. In this review, we summarize updated concepts by outlining the spectrum of anatomic locations of paragangliomas, the importance of morphology in establishing the correct diagnosis, the clinical implications for management, and the impact of genetics on the distinction between multifocal primary tumors compared with malignant disease. Full article

Background: Jugulotympanic paraganglioma (JTP) are benign, high-vascularized lesions that frequently invade the jugular foramen, temporal bone, the upper neck, and the posterior fossa cavity, resulting in a wide variety of clinical symptoms. Methods: In this retrospective study, we assess the clinical symptoms and discuss the individual multidisciplinary treatment and outcome of 22 patients with JTP. Results: In 12 patients, a hearing deficit was the presenting symptom, whereas pulsatile tinnitus and otalgia were present in six and four patients respectively. Facial nerve involvement was seen in six patients (three HB Grade 1–2 and three HB Grade 4–6). Four patients presented with lower cranial nerve impairment. Rare symptoms were ataxia caused by brainstem compression and papilledema due to cerebral sinus obstruction. A new or worsening of the preoperative facial nerve or lower cranial nerve function occurred in two and four patients respectively. Conclusion: The treatment strategy and the surgical approach for JTP should be tailored to the tumor extension and the patient’s clinical symptoms. Full article