ABSTRACT
Mediastinal paragangliomas are rare neuroendocrine tumors and usually identified incidentally. Surgical excision remains the mainstay of treatment. Because of their location, anatomical relations, and highly vascular nature, surgical excision can be challenging. We present such a case, where the blood supply arose directly from the circumflex coronary artery and cardiopulmonary bypass was used to aid complete surgical excision.
Subject(s)
Coronary Vessels , Mediastinal Neoplasms/blood supply , Paraganglioma/blood supply , Aged , Cardiopulmonary Bypass , Female , Humans , Mediastinal Neoplasms/surgery , Paraganglioma/surgerySubject(s)
Abdominal Neoplasms , Paraganglioma , Abdominal Neoplasms/blood supply , Abdominal Neoplasms/diagnostic imaging , Abdominal Neoplasms/surgery , Humans , Kidney/surgery , Male , Middle Aged , Nephrectomy , Paraganglioma/blood supply , Paraganglioma/diagnostic imaging , Paraganglioma/surgery , Renal Veins/surgery , Vena Cava, Inferior/surgerySubject(s)
Embolization, Therapeutic/methods , Paraganglioma/therapy , Preoperative Care/methods , Skull Neoplasms/therapy , Adult , Humans , Male , Ophthalmic Artery/surgery , Paraganglioma/blood supply , Paraganglioma/secondary , Skull/blood supply , Skull/pathology , Skull/surgery , Skull Neoplasms/blood supply , Skull Neoplasms/pathologyABSTRACT
Dopamine is a catecholamine that acts both as a neurotransmitter and as a hormone, exerting its functions via dopamine (DA) receptors that are present in a broad variety of organs and cells throughout the body. In the circulation, DA is primarily stored in and transported by blood platelets. Recently, the important contribution of DA in the regulation of angiogenesis has been recognized. In vitro and in vivo studies have shown that DA inhibits angiogenesis through activation of the DA receptor type 2. Overproduction of catecholamines is the biochemical hallmark of pheochromocytoma (PCC) and paraganglioma (PGL). The increased production of DA has been shown to be an independent predictor of malignancy in these tumors. The precise relationship underlying the association between DA production and PCC and PGL behavior needs further clarification. Herein, we review the biochemical and physiologic aspects of DA with a focus on its relations with VEGF and hypoxia inducible factor related angiogenesis pathways, with special emphasis on DA producing PCC and PGL.-Osinga, T. E., Links, T. P., Dullaart, R. P. F., Pacak, K., van der Horst-Schrivers, A. N. A., Kerstens, M. N., Kema, I. P. Emerging role of dopamine in neovascularization of pheochromocytoma and paraganglioma.
Subject(s)
Dopamine/metabolism , Neovascularization, Pathologic/metabolism , Paraganglioma/blood supply , Pheochromocytoma/blood supply , Adrenal Gland Neoplasms/metabolism , Adrenal Gland Neoplasms/pathology , Animals , Humans , Paraganglioma/pathology , Pheochromocytoma/metabolism , Pheochromocytoma/pathologyABSTRACT
SUMMARY Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL. During 101 weeks of therapy at different doses, sunitinib was able to cause a partial response and then a stable disease for a total of 78 weeks. This favorable response is the longest, out of the 35 so far reported in the literature, registered in a patient treated exclusively with sunitinib but, similarly to the other responses, the effect was limited in time. From our analysis of the scanty data present in the literature, the effect of sunitinib does not seem to be different among wild-type patients and those carrying a cluster 1 germ-line mutation. Sunitinib seems able to slow the disease progression in some patients with malignant PHEO/PGL and therefore may represent a therapeutic option, although randomized controlled studies are needed to assess its efficacy definitively in the treatment of these aggressive tumors.
Subject(s)
Humans , Male , Adult , Paraganglioma/drug therapy , Pyrroles/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Indoles/therapeutic use , Mutation/genetics , Antineoplastic Agents/therapeutic use , Paraganglioma/genetics , Paraganglioma/blood supply , Succinate Dehydrogenase/genetics , Treatment Outcome , Sunitinib , Neoplasm MetastasisABSTRACT
Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL. During 101 weeks of therapy at different doses, sunitinib was able to cause a partial response and then a stable disease for a total of 78 weeks. This favorable response is the longest, out of the 35 so far reported in the literature, registered in a patient treated exclusively with sunitinib but, similarly to the other responses, the effect was limited in time. From our analysis of the scanty data present in the literature, the effect of sunitinib does not seem to be different among wild-type patients and those carrying a cluster 1 germ-line mutation. Sunitinib seems able to slow the disease progression in some patients with malignant PHEO/PGL and therefore may represent a therapeutic option, although randomized controlled studies are needed to assess its efficacy definitively in the treatment of these aggressive tumors.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Indoles/therapeutic use , Mutation/genetics , Paraganglioma/drug therapy , Pyrroles/therapeutic use , Succinate Dehydrogenase/genetics , Adult , Humans , Male , Neoplasm Metastasis , Paraganglioma/blood supply , Paraganglioma/genetics , Sunitinib , Treatment OutcomeABSTRACT
A 60-year-old male patient who previously underwent carotid and jugular paraganglioma resections was referred because of a mediastinal recurrence at the root of the great vessels. Coronary angiography confirmed the circumflex artery of the left coronary artery as the feeding artery of the tumour. The patient underwent surgery due to the tumour's location and malignant potential. Upon mass resection, histopathological examination characterized the tumour as a secondary paraganglioma. Neuroendocrine tumours arising from chromaffin tissues at the extra-adrenal paraganglions of the autonomic nervous system are termed paragangliomas. Clinically, they are divided into functional and non-functional types, depending on their catecholamine secretion. The mediastinal location is exceptional and its treatment is challenging.
Subject(s)
Coronary Vessels/diagnostic imaging , Mediastinal Neoplasms/blood supply , Paraganglioma/blood supply , Coronary Angiography , Humans , Magnetic Resonance Imaging , Male , Mediastinal Neoplasms/diagnosis , Middle Aged , Neoplasm Recurrence, Local , Paraganglioma/diagnosis , Tomography, X-Ray ComputedSubject(s)
Glottis/blood supply , Laryngeal Neoplasms/blood supply , Paraganglioma/blood supply , Deglutition Disorders/etiology , Glottis/pathology , Glottis/surgery , Humans , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/surgery , Laryngoscopy , Magnetic Resonance Imaging , Male , Middle Aged , Paraganglioma/pathology , Paraganglioma/surgeryABSTRACT
Pheochromocytomas (PCC) and sympathetic paragangliomas (PGL) are rare neuroendocrine tumors, which derive from chromaffin cells occurring in the adrenal medulla and extra-adrenal sympathetic paraganglia. PCC and PGL are often benign, catecholamine-producing tumors, responsible for a myriad of symptoms that may be potentially hazardous to the patient. In contrast, nonsecreting parasympathetic PGL, derived from chief cells, develop mainly in the head and neck region. Although PCC/PGL are more commonly sporadic tumors, germline mutations are present in up to 40% of the patients, ranking these tumors among those with the highest degree of heritability. PCC/PGL are associated with a variety of hereditary syndromes, comprising genetic alterations in RET, NF1, VHL, and SDHx genes, the last 2 being involved in regulating the hypoxia pathway. Additional hypoxia pathway-related genes have been recently associated with PCC/PGL development, namely EGLN1 and EPAS1. Thus, dysregulation of the hypoxia pathway seems to play a major role in PCC/PGL development, in particular through the stabilization of hypoxia-inducible factors and the appearance of a pseudohypoxia signature. This article is focused on reviewing the tumorigenic mechanisms resultant from VHL, SDHx, EGLN1, and EPAS1 mutations, as well as the associated tumors, namely PCC/PGL, and extra manifestations such as polycythemia. In the light of the recent discoveries, hypoxia pathway molecules appear as key players in PCC/PGL development.
Subject(s)
Cell Hypoxia/genetics , Mutation , Paraganglioma/genetics , Pheochromocytoma/genetics , Humans , Neovascularization, Pathologic , Paraganglioma/blood supply , Paraganglioma/pathology , Pheochromocytoma/blood supply , Pheochromocytoma/pathologyABSTRACT
Pheochromocytomas (PCCs) are neuroendocrine tumors arising from chromaffin cells of the adrenal medulla. Related tumors that arise from the paraganglia outside the adrenal medulla are called paragangliomas (PGLs). PCC/PGLs are usually benign, but approximately 17% of these tumors are malignant, as defined by the development of metastases. Currently, there are no generally accepted markers for identifying a primary PCC or PGL as malignant. In 2002, Favier et al. described the use of vascular architecture for the distinction between benign and malignant primary PCC/PGLs. The aim of this study was to validate the use of vascular pattern analysis as a test for malignancy in a large series of primary PCC/PGLs. Six independent observers scored a series of 184 genetically well-characterized PCCs and PGLs for the CD34 immunolabeled vascular pattern and these findings were correlated to the clinical outcome. Tumors were scored as malignant if an irregular vascular pattern was observed, including vascular arcs, parallels and networks, while tumors with a regular pattern of short straight capillaries were scored as benign. Mean sensitivity and specificity of vascular architecture, as a predictor of malignancy was 59.7% and 72.9%, respectively. There was significant agreement between the 6 observers (mean κ = 0.796). Mean sensitivity of vascular pattern analysis was higher in tumors >5 cm (63.2%) and in genotype cluster 2 tumors (100%). In conclusion, vascular pattern analysis cannot be used in a stand-alone manner as a prognostic tool for the distinction between benign and malignant PCC, but could be used as an indicator of malignancy and might be a useful tool in combination with other morphological characteristics.
Subject(s)
Adrenal Gland Neoplasms/blood supply , Adrenal Gland Neoplasms/pathology , Paraganglioma/blood supply , Paraganglioma/pathology , Pheochromocytoma/blood supply , Pheochromocytoma/pathology , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Observer Variation , Prognosis , Young AdultSubject(s)
Heart Neoplasms/diagnostic imaging , Heart Ventricles/diagnostic imaging , Paraganglioma/diagnostic imaging , Adult , Coronary Angiography , Echocardiography , Female , Heart Neoplasms/blood supply , Heart Neoplasms/pathology , Heart Ventricles/pathology , Humans , Paraganglioma/blood supply , Paraganglioma/pathologySubject(s)
Mesentery/diagnostic imaging , Neoplasms, Multiple Primary/diagnostic imaging , Ovarian Neoplasms/diagnostic imaging , Paraganglioma/diagnostic imaging , Peritoneal Neoplasms/diagnostic imaging , Teratoma/diagnostic imaging , Biomarkers, Tumor/analysis , Female , Humans , Incidental Findings , Ki-67 Antigen/analysis , Laparoscopy , Mesenteric Cyst/diagnostic imaging , Mesenteric Cyst/surgery , Middle Aged , Ovarian Neoplasms/surgery , Paraganglioma/blood supply , Paraganglioma/chemistry , Paraganglioma/surgery , Peritoneal Neoplasms/blood supply , Peritoneal Neoplasms/chemistry , Peritoneal Neoplasms/surgery , Teratoma/surgery , UltrasonographySubject(s)
Embolization, Therapeutic/methods , Neovascularization, Pathologic/therapy , Adult , Dopamine , Heart Neoplasms/blood supply , Heart Neoplasms/diagnosis , Heart Neoplasms/pathology , Heart Neoplasms/therapy , Humans , Male , Paraganglioma/blood supply , Paraganglioma/diagnosis , Paraganglioma/pathology , Paraganglioma/therapyABSTRACT
OBJECTIVE: To describe primary paraganglioma in the facial nerve canal and discuss the characteristics of facial nerve paraganglioma in contrast with other tumors. CASE REPORT: A 23-year-old man developed gradually progressive right facial palsy as the initial symptom. One year later, he exhibited hearing loss without tinnitus in his right ear. CT demonstrated an enlarged facial nerve canal with irregular bony erosion of the circumference. MRI showed a well-enhanced heterogeneous mass with hypo-intensity spots inside it. During surgery, a blood-rich tumor was observed along the facial nerve: however, extensive bleeding interfered with tumor removal. The surgical specimen demonstrated paraganglioma. The tumor was completely removed in the second surgery in combination with arterial embolization. Facial nerve function was reconstructed with a free muscle flap more than one year following resection. CONCLUSION: Because paraganglioma is a blood-rich tumor, it is important to perform angiography and embolization. If preoperative facial nerve palsy is demonstrated, careful management of facial nerve function is needed. Paraganglioma must be considered in the differential diagnosis of a facial nerve tumor.
Subject(s)
Cranial Nerve Neoplasms/surgery , Facial Nerve Diseases/surgery , Paraganglioma/surgery , Cranial Nerve Neoplasms/blood supply , Cranial Nerve Neoplasms/diagnostic imaging , Embolization, Therapeutic , Facial Nerve Diseases/diagnostic imaging , Humans , Male , Paraganglioma/blood supply , Paraganglioma/diagnostic imaging , Tomography, X-Ray Computed , Young AdultSubject(s)
Catheter Ablation , Heart Neoplasms/surgery , Paraganglioma/surgery , Pulmonary Veins/surgery , Atrial Fibrillation/etiology , Coronary Angiography , Echocardiography , Female , Heart Atria/pathology , Heart Neoplasms/blood supply , Heart Neoplasms/diagnosis , Humans , Middle Aged , Paraganglioma/blood supply , Paraganglioma/diagnosis , Pulmonary Veins/pathology , Tomography, X-Ray ComputedSubject(s)
Heart Neoplasms/diagnosis , Heart Neoplasms/surgery , Heart Septum/surgery , Paraganglioma/diagnosis , Paraganglioma/surgery , Biomarkers, Tumor/analysis , Coronary Angiography , Coronary Vessels , Echocardiography , Female , Heart Atria/pathology , Heart Atria/surgery , Heart Neoplasms/blood supply , Heart Neoplasms/pathology , Heart Septum/pathology , Humans , Image Interpretation, Computer-Assisted , Imaging, Three-Dimensional , Middle Aged , Paraganglioma/blood supply , Paraganglioma/pathology , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Paraganglioma is a rare but highly vascular tumor of the anterior mediastinum. Surgical resection is a challenge owing to the close proximity to vital structures including the heart, trachea and great vessels. Preoperative embolization has been reported once to facilitate surgical treatment. CASE PRESENTATION: We report a case of anterior mediastinal paraganglioma that was embolized preoperatively, and was resected without the need for cardiopulmonary bypass and without major bleeding complications. CONCLUSION: We make a case to further the role of preoperative embolization in the treatment of mediastinal paragangliomas.
Subject(s)
Blood Loss, Surgical/prevention & control , Embolization, Therapeutic , Mediastinal Neoplasms/surgery , Paraganglioma/surgery , Preoperative Care/methods , Humans , Mediastinal Neoplasms/blood supply , Middle Aged , Paraganglioma/blood supplyABSTRACT
Tympanic paragangliomas usually present as a vascular middle ear mass, with the most common presenting symptoms being pulsatile tinnitus and hearing loss. We report an unusual case of a recurrent tympanic paraganglioma extending along the Eustachian tube and nasopharynx, presenting with recurrent epistaxis.
Subject(s)
Ear Neoplasms/pathology , Ear, Middle/pathology , Eustachian Tube/pathology , Nasopharynx/pathology , Paraganglioma/pathology , Ear Neoplasms/blood supply , Ear Neoplasms/complications , Ear Neoplasms/diagnostic imaging , Ear Neoplasms/surgery , Ear, Middle/diagnostic imaging , Ear, Middle/surgery , Endoscopy , Epistaxis/etiology , Eustachian Tube/diagnostic imaging , Female , Humans , Middle Aged , Nasopharynx/diagnostic imaging , Neoplasm Invasiveness , Neoplasm Recurrence, Local/surgery , Paraganglioma/blood supply , Paraganglioma/complications , Paraganglioma/diagnostic imaging , Paraganglioma/surgery , Radiosurgery , Tomography, X-Ray ComputedSubject(s)
Central Nervous System Neoplasms/pathology , Microvessels/pathology , Astrocytoma/blood supply , Astrocytoma/pathology , Capillaries/pathology , Central Nervous System Neoplasms/blood supply , Diagnosis, Differential , Ependymoma/blood supply , Ependymoma/pathology , Glioblastoma/blood supply , Glioblastoma/pathology , Hemangioblastoma/blood supply , Hemangioblastoma/pathology , Humans , Hyperplasia , Neoplasms, Neuroepithelial/blood supply , Neoplasms, Neuroepithelial/pathology , Oligodendroglioma/blood supply , Oligodendroglioma/pathology , Paraganglioma/blood supply , Paraganglioma/pathologyABSTRACT
Primary cardiac paraganglioma (pheochromocytoma) is very rare, constituting only 1% of cardiac tumours. A case of a 44-year-old woman presenting with angina chest pain and a tumour with dual blood supply from both the right and left coronary arteries is reported.