Intrathoracic carotid-body tumour (chemodectoma).

Ashley, David J. B.; Evans, C. Lawrence

doi:10.1136/thx.21.2.184

Cited by 11 publications

(3 citation statements)

References 7 publications

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“…Using light microscopy, a ‘clear cell’ phenotype was observed in approximately half of the hyperplastic CBs (Fig. C , lower), similar to the vacuolated cytoplasm observed in carotid paragangliomas (Ashley & Evans, ; Robertson & Cooney, ; Wieneke & Smith, ) and enlarged CBs from high altitude dwellers (Edwards et al . ; Edwards et al .…”

Section: Resultssupporting

confidence: 66%

“…Although we have not formally demonstrated this, our observation of very high levels of Vegfa mRNA in Type I cells would be consistent with that hypothesis. Second, the enlarged CBs frequently showed a ‘clear cell’ phenotype by light microscopy, resembling the typical vacuolated histology of Type I cells in human paraganglioma (Ashley & Evans, ; Robertson & Cooney, ; Kliewer et al . ; Wieneke & Smith, ).…”

Section: Discussionmentioning

confidence: 80%

“…The enlarged CBs associated with Type I cell restricted PHD2 inactivation also manifest several features that are reminiscent of human paraganglioma (Ashley & Evans, ; Robertson & Cooney, ; Kliewer et al . ; Jyung et al .…”

Section: Discussionmentioning

confidence: 99%

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PHD2 inactivation in Type I cells drives HIF‐2α‐dependent multilineage hyperplasia and the formation of paraganglioma‐like carotid bodies

Fielding

Hodson

Cheng

et al. 2018

The Journal of Physiology

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Key points The carotid body is a peripheral arterial chemoreceptor that regulates ventilation in response to both acute and sustained hypoxia.Type I cells in this organ respond to low oxygen both acutely by depolarization and dense core vesicle secretion and, over the longer term, via cellular proliferation and enhanced ventilatory responses.Using lineage analysis, the present study shows that the Type I cell lineage itself proliferates and expands in response to sustained hypoxia.Inactivation of HIF‐2α in Type I cells impairs the ventilatory, proliferative and cell intrinsic (dense core vesicle) responses to hypoxia.Inactivation of PHD2 in Type I cells induces multilineage hyperplasia and ultrastructural changes in dense core vesicles to form paraganglioma‐like carotid bodies.These changes, similar to those observed in hypoxia, are dependent on HIF‐2α.Taken together, these findings demonstrate a key role for the PHD2–HIF‐2α couple in Type I cells with respect to the oxygen sensing functions of the carotid body. AbstractThe carotid body is a peripheral chemoreceptor that plays a central role in mammalian oxygen homeostasis. In response to sustained hypoxia, it manifests a rapid cellular proliferation and an associated increase in responsiveness to hypoxia. Understanding the cellular and molecular mechanisms underlying these processes is of interest both to specialized chemoreceptive functions of that organ and, potentially, to the general physiology and pathophysiology of cellular hypoxia. We have combined cell lineage tracing technology and conditionally inactivated alleles in recombinant mice to examine the role of components of the HIF hydroxylase pathway in specific cell types within the carotid body. We show that exposure to sustained hypoxia (10% oxygen) drives rapid expansion of the Type I, tyrosine hydroxylase expressing cell lineage, with little transdifferentiation to (or from) that lineage. Inactivation of a specific HIF isoform, HIF‐2α, in the Type I cells was associated with a greatly reduced proliferation of Type I cells and hypoxic ventilatory responses, with ultrastructural evidence of an abnormality in the action of hypoxia on dense core secretory vesicles. We also show that inactivation of the principal HIF prolyl hydroxylase PHD2 within the Type I cell lineage is sufficient to cause multilineage expansion of the carotid body, with characteristics resembling paragangliomas. These morphological changes were dependent on the integrity of HIF‐2α. These findings implicate specific components of the HIF hydroxylase pathway (PHD2 and HIF‐2α) within Type I cells of the carotid body with respect to the oxygen sensing and adaptive functions of that organ.

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Section: Resultssupporting

confidence: 66%

Section: Discussionmentioning

confidence: 80%

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PHD2 inactivation in Type I cells drives HIF‐2α‐dependent multilineage hyperplasia and the formation of paraganglioma‐like carotid bodies

Fielding

Hodson

Cheng

et al. 2018

The Journal of Physiology

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Intrathoracic Paraganglioma Arising From Aorticosympathetic Paraganglion

Arom¹

1976

Arch Surg

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Mediastinal paragangliomas (Aortic body tumor).A report of four cases and a review of the literature

Olson

Salyer

1978

Cancer

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Four cases of paraganglioma originating in the supra-aortic or aortico-pulmonary bodies are described. A review of the reported examples of aortic body tumors and a study of these four cases indicate that there is a high incidence of aggressive tumor growth in the mediastinum, with resultant important morbidity or death in 16 of 35 cases. The morphologic features of aortic body tumors are identical to those of paragangliomas of other locations, and the occurrence of invasive growth and/or metastasis cannot be predicted on histologic grounds.Cancer 4 1 : 2405-24 12, 1978. N 1950 LATTES REPORTED TWO EXAMPLES OFI paragangliomas originating in the area of the aortic arch. Since that time an additional 47 mediastinal paragangliomas have been described. Twelve of these were located in the costo-vertebral sulcus (mediastinal aortico-sympathetic paraganglioma). The remaining 35 tumors and the four described in this report originated in the area of the aortic arch and are classified as aortico-pulmonary paragangliomas as defined by Glenner and Grimley. Review of these cases revealed a high incidence of morbidity and death associated with aortic body paragangliomas, largely due to invasive growth of residual mediastinal neoplasm. CASE REPORTS Case 1A normotensive 37-year-old woman was found to have mediastinal mass on routine chest x-ray in 1951. The lesion was contiguous with the aortic arch. In 1954 surgical removal of the lesion was attempted, but only partial excision of the mass was possible. Following surgery, radiotherapy resulted in initial reduction in the size of the residual tumor. The tumor slowly progressed, however, leading to respiratory insufficiency and death 13 years after the original chest x-ray. At autopsy extensive local infiltration of the mediastinum by tumor was noted. Metastases were not identified. Case 2A 51-year-old man with a 1 Yi history of cough developed hemoptysis and left chest pain. He had decreased breath sounds in the anterior left upper chest and deviation of the trachea to the right. At the time of admission the chest x-ray demonstrated a rounded density in the anterior superior mediastinum and in the left hilum. Review of previous radiographs revealed that a mass had been present for three years. At thoracotomy an extremely vascular tumor was observed in the left anterolateral aspect of the mediastinum. It was adherent to the lung and had invaded the innominate vein, adventitia of aortic arch, and anterior chest wall. The patient died intraoperatively secondary to hemorrhage from the tumor. Both routine laboratory studies and skeletal survey were within normal limits. Permission for an autopsy was denied. .Case 3In 1960 a 55-year-old man presented with the superior vena cava syndrome. H e was known to have had a widened medastinum for the previous five years but had been asymptomatic during that period. At thoracotomy in 1960 tumor involved the superior vena cava, right and left phrenic nerves, and aorta. A partial excision was performed. At a second thoracotomy in 1963, tumor occl...

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Intrathoracic carotid-body tumour (chemodectoma).

Cited by 11 publications

References 7 publications

PHD2 inactivation in Type I cells drives HIF‐2α‐dependent multilineage hyperplasia and the formation of paraganglioma‐like carotid bodies

PHD2 inactivation in Type I cells drives HIF‐2α‐dependent multilineage hyperplasia and the formation of paraganglioma‐like carotid bodies

Intrathoracic Paraganglioma Arising From Aorticosympathetic Paraganglion

Mediastinal paragangliomas (Aortic body tumor).A report of four cases and a review of the literature

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