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BMJ Case Reports Jul 2021Vagal paragangliomas (VPs) are a rare subset of neuroendocrine tumour derived from paraganglia located in the head/neck that are usually indolent in nature. Typical...
Vagal paragangliomas (VPs) are a rare subset of neuroendocrine tumour derived from paraganglia located in the head/neck that are usually indolent in nature. Typical clinical presentations include pulsatile tinnitus or hoarseness associated with a neck mass. Surgery and radiation therapy remain the primary treatment modalities but come with significant morbidity including cranial nerve damage. We describe a unique case of VP in which cough was the only presenting symptom, that was exacerbated by enlargement of the tumour. Symptoms improved following radiation treatment.
Topics: Cough; Cranial Nerve Neoplasms; Head and Neck Neoplasms; Humans; Paraganglioma; Paraganglioma, Extra-Adrenal
PubMed: 34330721
DOI: 10.1136/bcr-2021-241913 -
Autopsy & Case Reports 2021Paragangliomas are rare, encapsulated, benign neuroendocrine tumors that can arise from the adrenal medulla or extra-adrenal paraganglia. Extra-adrenal paragangliomas...
Paragangliomas are rare, encapsulated, benign neuroendocrine tumors that can arise from the adrenal medulla or extra-adrenal paraganglia. Extra-adrenal paragangliomas may develop a gangliocytic component with ganglion cells (Gangliocytic paragangliomas). Nearly 25%of cauda equina paragangliomas are gangliocytic paragangliomas. Here, we describe the case of a 35-year-old male who presented with weakness of both lower limbs over the last two months. Radiological findings were suggestive of myxopapillary ependymoma. However, the histopathological examination revealed a tumor with cells arranged in sheets, papillae, lobules, and around vessels forming pseudo rosettes. Ganglion cells were seen in small groups and, also singly. Tumor cells were immunopositive for chromogranin, synaptophysin, and S-100. Ganglion cells were immunopositive for synaptophysin, NSE, and NFP. A final histological diagnosis of Gangliocytic paraganglioma (WHO grade I) was made. To date, only nine gangliocytic paraganglioma cases have been previously reported, and to the best of our knowledge, this is the largest gangliocytic paraganglioma.
PubMed: 34307231
DOI: 10.4322/acr.2021.277 -
Frontiers in Oncology 2021Paragangliomas (PGLs) are neuroendocrine neoplasms arising from chromaffin cells of sympathetic or parasympathetic paraganglia. Systemic therapies have been used only in...
BACKGROUND
Paragangliomas (PGLs) are neuroendocrine neoplasms arising from chromaffin cells of sympathetic or parasympathetic paraganglia. Systemic therapies have been used only in metastatic PGLs. Antiangiogenic agents, such as sunitinib, could be a viable therapeutic choice in the subgroup of patients with -positive PGLs. We describe the case of a man with Familial Paraganglioma Syndrome type 1 (FPGL) related to a novel mutation in gene treated with sunitinib. Furthermore, we performed a systematic review of the literature aimed to address the following question: is sunitinib treatment effective in patients with advanced/progressive/metastatic PGL?
METHODS
We performed a data search using MEDLINE, Cochrane Library, and Scopus between April 2019 and September 2020. We included studies reporting data on clinical or biological characteristics, or clinical outcomes of patients with PGLs treated with sunitinib.
RESULTS
The search leaded to the selection of 25 publications. Data from case reports and case series showed that disease control rate (DCR = stable disease + partial response + complete response) was achieved in 34.7% of cases under sunitinib treatment. In 39% of patients DCR was followed by progressive disease (PD) or tumor relapse, 26.1% patients showed PD. Data from clinical trials showed that DCR was 83%, and the median progression free survival was 13.4 months.
DISCUSSION
Data from the present literature review suggested that sunitinib could be a viable therapeutic option in advanced/progressive/metastatic inoperable PGLs. However, further trials on the efficacy of sunitinib in FPGL and sporadic PGL are needed.
PubMed: 34221997
DOI: 10.3389/fonc.2021.677983 -
Veterinary Sciences May 2021Paraganglioma is a rare neuroendocrine neoplasm originating from paraganglia and consisting of neuroendocrine cells of the sympathetic and parasympathetic nervous...
Paraganglioma is a rare neuroendocrine neoplasm originating from paraganglia and consisting of neuroendocrine cells of the sympathetic and parasympathetic nervous system. Extra-adrenal paraganglioma occurs with a low incidence in both humans and animals. This report presents the first case of paraganglioma in a cat with orbital primary location. An 18-year-old spayed female European domestic shorthair cat of 3.60 kg body weight was evaluated in a private veterinary clinic in Perugia, Italy, for a pronounced exophthalmos of the right eye. The cat underwent surgery for the enucleation of the right eye and of the mass. The biopsy samples of the removed tissue were fixed in 10% buffered neutral formalin for histological and immunohistochemical evaluations. Therefore, specific markers were used for immunohistochemical investigations, such as anti-neuron specific enolase (NSE), anti-synaptophysin, anti-glial fibrillary acid protein, anti-cytokeratin and anti-chromogranin. The results of these investigations allowed establishing the final diagnosis of ocular extra-adrenal paraganglioma of the cat.
PubMed: 34068893
DOI: 10.3390/vetsci8050086 -
Journal of Ultrasound Sep 2021Paragangliomas are a rare form of highly vascularized tumors that originate from paraganglia Baysal (J Med Genet 39: 617-622, 2002). In the head and neck PGL arise...
Paragangliomas are a rare form of highly vascularized tumors that originate from paraganglia Baysal (J Med Genet 39: 617-622, 2002). In the head and neck PGL arise primarily in four distinct areas: vagal, middle ear, and larynx and more frequently carotid bifurcation. Imaging evaluations include sonography, color Doppler, US-elastosonography and contrast-enhanced ultrasound (CEUS). Additionally, Computed Tomography, Magnetic Resonance Imaging (MRI) as well as digital subtraction angiography can be performed Stoeckli et al. (Laryngoscope 112: 143-146, 2002). We present herein a case of a rare bilateral carotid body tumor assessed with multiparametric ultrasound evaluation, including CEUS and US-elastography.
Topics: Angiography, Digital Subtraction; Carotid Body Tumor; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Ultrasonography
PubMed: 33999368
DOI: 10.1007/s40477-021-00581-z -
Cell Death & Disease May 2021Pheochromocytoma/paraganglioma (PPGL) is an endocrine tumor of the chromaffin cells in the adrenal medulla or the paraganglia. Currently, about 70% of PPGLs can be...
GIPC2 is an endocrine-specific tumor suppressor gene for both sporadic and hereditary tumors of RET- and SDHB-, but not VHL-associated clusters of pheochromocytoma/paraganglioma.
Pheochromocytoma/paraganglioma (PPGL) is an endocrine tumor of the chromaffin cells in the adrenal medulla or the paraganglia. Currently, about 70% of PPGLs can be explained by germline or somatic mutations in several broadly expressed susceptibility genes including RET, VHL, and SDHB, while for the remaining, mainly sporadic cases, the pathogenesis is still unclear. Even for known susceptible genes, how mutations in these mostly ubiquitous genes result in tissue-specific pathogenesis remains unanswered, and why RET-mutated tumors almost always occur in the adrenal while SDHB-mutated tumors mostly occur extra-adrenal remains a mystery. By analyzing 22 sporadic PPGLs using SNP 6.0 genotyping arrays combined with expression profiling of 4 normal and 4 tumor tissues, we identified GIPC2, a gene located at 1p31.1 with preferential expression in adrenal and inducible by adrenal glucocorticoid, as a novel putative tumor suppressor gene for PPGLs. Copy number deletion and GIPC2 promoter hypermethylation but not GIPC2 mutation, accompanied with reduced GIPC2 expression, were observed in 39 of 55 PPGLs in our cohort. Examination of a published expression database consisting of 188 PPGLs found little GIPC2 expression in Cluster 1A (SDHx-associated) and Cluster 2A (NF1/RET-associated) tumors, but less pronounced reduction of GIPC2 expression in Cluster 1B (VHL-associated) and Cluster 2B/2C tumors. GIPC2 induced p27, suppressed MAPK/ERK and HIF-1ɑ pathways as well as cancer cell proliferation. Overexpressing GIPC2 in PC12 cells inhibited tumor growth in nude mice. We found GIPC2 interacted with the nucleoprotein NONO and both proteins regulated p27 transcription through the same GGCC box on p27 promoter. Significantly, low expression of both GIPC2 and p27 was associated with shorter disease-free survival time of PPGLs patients in the TCGA database. We found that PPGL-causing mutations in RET and in SDHB could lead to primary rat adrenal chromaffin cell proliferation, ERK activation, and p27 downregulation, all requiring downregulating GIPC2. Notably, the RET-mutant effect required the presence of dexamethasone while the SDHB-mutant effect required its absence, providing a plausible explanation for the tumor location preference. In contrast, the PPGL-predisposing VHL mutations had no effect on proliferation and GIPC2 expression but caused p53 downregulation and reduced apoptosis in chromaffin cells compared with wild-type VHL. Thus, our study raises the importance of cortical hormone in PPGL development, and GIPC2 as a novel tumor suppressor provides a unified molecular mechanism for the tumorigenesis of both sporadic and hereditary tumors of Clusters 1A and 2A concerning SDHB and RET, but not tumors of Cluster 1B concerning VHL and other clusters.
Topics: Adrenal Gland Neoplasms; Carrier Proteins; Genes, Tumor Suppressor; Humans; Pheochromocytoma; Proto-Oncogene Proteins c-ret; Succinate Dehydrogenase; Transfection
PubMed: 33947839
DOI: 10.1038/s41419-021-03731-7 -
Frontiers in Endocrinology 2021Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia....
INTRODUCTION
Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor () gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious variant associated with hereditary pheochromocytoma in a family with four affected individuals.
CASE PRESENTATION
The first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the gene.
CONCLUSION
This case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Age of Onset; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Family; Fatal Outcome; Genetic Association Studies; Genetic Testing; Germ-Line Mutation; Humans; Male; Neoplasms, Multiple Primary; Neuroblastoma; Pheochromocytoma; Portugal
PubMed: 33815275
DOI: 10.3389/fendo.2021.609263 -
The Journal of International Medical... Mar 2021A paraganglioma is an extra-adrenal tumor of the paraganglia often found in association with sympathetic and parasympathetic nerves. A primary pulmonary paraganglioma...
A paraganglioma is an extra-adrenal tumor of the paraganglia often found in association with sympathetic and parasympathetic nerves. A primary pulmonary paraganglioma generally presents as multiple small tumors or a solitary mass; however, endobronchial involvement is extremely rare. A 49-year-old man was admitted to our hospital because of a chronic cough, intermittent dyspnea, and chest pain. Chest computed tomography revealed a rounded, high-density lesion in the left lower lung lobe. Fiberoptic bronchoscopy demonstrated an endobronchial mass characterized by smooth, hypervascularized mucosa. Transbronchial biopsy of the mass and immunohistochemistry results suggested a paraganglioma. The patient fully recovered after lobectomy and lymphadenectomy. Pulmonary paragangliomas are rarely reported. Complete surgical resection is considered the treatment of choice for pulmonary paragangliomas, and the long-term prognosis is generally good. However, life-long follow-up is mandatory because of the possibility of recurrence and metastasis. This case report adds valuable knowledge to the literature on pulmonary paragangliomas.
Topics: Bronchoscopy; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Paraganglioma; Tomography, X-Ray Computed
PubMed: 33771069
DOI: 10.1177/03000605211003014 -
Endocrine Pathology Jun 2021Abdominal paragangliomas and pheochromocytomas (PPGLs) are rare neuroendocrine tumors of the infradiaphragmatic paraganglia and adrenal medulla, respectively. Although... (Review)
Review
Abdominal paragangliomas and pheochromocytomas (PPGLs) are rare neuroendocrine tumors of the infradiaphragmatic paraganglia and adrenal medulla, respectively. Although few pathologists outside of endocrine tertiary centers will ever diagnose such a lesion, the tumors are well known through the medical community-possible due to a combination of the sheer rarity, their often-spectacular presentation due to excess catecholamine secretion as well as their unrivaled coupling to constitutional susceptibility gene mutations and hereditary syndromes. All PPGLs are thought to harbor malignant potential, and therefore pose several challenges to the practicing pathologist. Specifically, a responsible diagnostician should recognize both the capacity and limitations of histological, immunohistochemical, and molecular algorithms to pinpoint high risk for future metastatic disease. This focused review aims to provide the surgical pathologist with a condensed update regarding the current strategies available in order to deliver an accurate prognostication of these enigmatic lesions.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Humans; Immunohistochemistry; Paraganglioma; Pathology, Molecular; Pheochromocytoma
PubMed: 33768452
DOI: 10.1007/s12022-021-09675-0 -
Frontiers in Endocrinology 2020Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells in the adrenal medulla (PCCs) or extra-adrenal sympathetic... (Review)
Review
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells in the adrenal medulla (PCCs) or extra-adrenal sympathetic or parasympathetic paraganglia (PGLs). About 40% of PPGLs result from germline mutations and therefore they are highly inheritable. Although dysfunction of any one of a panel of more than 20 genes can lead to PPGLs, mutations in genes involved in the VHL/HIF axis including , , , and are more frequently found in PPGLs. Multiple lines of evidence indicate that pseudohypoxia plays a crucial role in the tumorigenesis of PPGLs, and therefore PPGLs are also known as metabolic diseases. However, the interplay between VHL/HIF-mediated pseudohypoxia and metabolic disorder in PPGLs cells is not well-defined. In this review, we will first discuss the VHL/HIF axis and genetic alterations in this axis. Then, we will dissect the underlying mechanisms in VHL/HIF axis-driven PPGL pathogenesis, with special attention paid to the interplay between the VHL/HIF axis and cancer cell metabolism. Finally, we will summarize the currently available compounds/drugs targeting this axis which could be potentially used as PPGLs treatment, as well as their underlying pharmacological mechanisms. The overall goal of this review is to better understand the role of VHL/HIF axis in PPGLs development, to establish more accurate tools in PPGLs diagnosis, and to pave the road toward efficacious therapeutics against metastatic PPGLs.
Topics: Adrenal Gland Neoplasms; Animals; Antineoplastic Agents; Apoptosis Regulatory Proteins; Basic Helix-Loop-Helix Transcription Factors; Chromaffin Cells; Germ-Line Mutation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Pheochromocytoma; Protein Kinase Inhibitors; Repressor Proteins; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 33329393
DOI: 10.3389/fendo.2020.586857