Pulmonary and mediastinal paragangliomas: rare endothoracic malignancies with challenging diagnosis and treatment

Abstract

Background: Pulmonary and mediastinal paragangliomas are rare tumors that may have neuroendocrine activity or be non-functional, incidental, in asymptomatic patients, or causing mass effect symptoms. Although being low-grade tumors, they can display an aggressive behaviour, developing local infiltration and distant metastases. We report our experience with three endothoracic paragangliomas and a Literature review, to point out diagnostic difficulties and problems related to surgical treatment.

Methods: From 2009 to 2017, we treated 3 patients with histological diagnosis of paraganglioma: 2 pulmonary, 1 mediastinal. No one presented catecholamine-secreting syndromes; pulmonary cases were asymptomatic, while the mediastinal one had aspecific cough and dyspnea. Imaging diagnosis was based on chest computerized tomography (CT) and magnetic resonance imaging (MRI) scan. No patient had preoperative histological diagnosis. Intraoperative pathological examination was suggestive for malignancy: in pulmonary cases, wedge resection and lobectomy were performed; the middle mediastinal mass was completely removed after challenging dissection, isolation and section of numerous vascular pedicles.

Results: Postoperative course was uneventful in all cases. No patient received adjuvant treatments. At a median follow-up of 47 months (range, 6-102 months), two patients are alive, without local or distant recurrence; one patient died 6 months after surgery, due to disease progression.

Conclusions: Endothoracic paragangliomas, rare and often asymptomatic tumors, are of difficult diagnosis and should be considered malignant tumors, due to the potential aggressive behaviour of cases with high mitotic index and the frequent possibility of recurrence and metastases. Surgical resection is the treatment of choice and careful intraoperative manipulation is recommended, due to the high vascularity of these tumors, to prevent complications. After complete excision, long-term prognosis is generally good. However, even after surgical removal, a close, periodical and life-long follow-up is mandatory.

Keywords: Paragangliomas; diagnosis; lung; mediastinum; surgical treatment.

Figure 1

Chest CT scan of middle mediastinal paraganglioma. (A,B) Chest CT scan showing a middle mediastinal paraganglioma (arrow), about 3.5 cm in diameter, adjacent to the superior vena cava, the aortic arch, the right branch of the pulmonary artery and the trachea; (C) contrast enhancement reveals vascular supply from the right subclavian and jugular veins (arrows). CT, computerized tomography.

Figure 2

Chest MRI scan showing a solid, hypervascularized, middle mediastinal paraganglioma, posteriorly to the ascending aorta and above the right pulmonary artery. MRI, magnetic resonance imaging.

Figure 3

Surgical resection of middle mediastinal paraganglioma. (A,B) Intraoperative identification, isolation (after section of numerous vascular pedicles) and (C,D) complete resection of a middle mediastinal paraganglioma.

Figure 4

Mediastinal paraganglioma: (A) haematoxylin-eosin 100× showing the peripheral capsule and a rich microvasculature; (B) haematoxylin-eosin 400× showing a typical pattern of nests of neoplastic epithelioid cells, with large hyperchromic nuclei, surrounded by thin-walled dilated vessels; (C) positive immunohistochemical staining for chromogranin A in the neoplastic cells, mostly prevalent at the perinuclear site (200×); (D) positive immunohistochemical staining for synaptophysin in almost 90% of the neoplastic cells, mostly prevalent at the cellular membrane (200×); (E) positive immunohistochemical staining for S-100 protein in the cytoplasm of the sustentacular cells, drawing a delicate net around the neoplastic cells (200×); (F) few neoplastic cells stain positively for Ki-67 (200×); note that many large hyperchromic nuclei do not result positive, revealing the degenerative nature of the phenomenon.

Figure 5

Pulmonary paraganglioma: (A) haematoxylin-eosin 100× showing a typical pattern of nests of monomorphic neoplastic cells, with scarce cytoplasm; an area of neoplastic coagulative necrosis is visible on the left; (B) a high number of proliferating neoplastic cells stain positively for Ki-67 (200×) and in this patient was associated with a negative prognosis.