Pheochromocytomas and Paragangliomas-Current Management

Abstract

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.

Keywords: SDHx mutation; adrenalectomy; carotid body tumor; jugulo-tympanic paraganglioma; paraganglioma; pheochromocytoma; stereotactic radiosurgery; vagal paraganglioma.

Figure 1

Division of paragangliomas according to the current WHO classification (2022).

Figure 2

(A) Histopathological picture: Hematoxylin and Eosin (H&E) in retroperitoneal paraganglioma in 52-year-old white male patient; (B) histopathological picture: Chromogranin A (CgA) (+++) in retroperitoneal paraganglioma in 52-year-old white male patient; (C) histopathological picture: Synaptophysin (++) in retroperitoneal paraganglioma in 52-year-old white male patient; (D) histopathological picture: S 100—focally positive in retroperitoneal paraganglioma in 52-year-old white male patient; and (E) histopathological picture: Ki-67 (2–3%) in retroperitoneal paraganglioma in 52-year-old white male patient.

Figure 2

(A) Histopathological picture: Hematoxylin and Eosin (H&E) in retroperitoneal paraganglioma in 52-year-old white male patient; (B) histopathological picture: Chromogranin A (CgA) (+++) in retroperitoneal paraganglioma in 52-year-old white male patient; (C) histopathological picture: Synaptophysin (++) in retroperitoneal paraganglioma in 52-year-old white male patient; (D) histopathological picture: S 100—focally positive in retroperitoneal paraganglioma in 52-year-old white male patient; and (E) histopathological picture: Ki-67 (2–3%) in retroperitoneal paraganglioma in 52-year-old white male patient.

Figure 2

(A) Histopathological picture: Hematoxylin and Eosin (H&E) in retroperitoneal paraganglioma in 52-year-old white male patient; (B) histopathological picture: Chromogranin A (CgA) (+++) in retroperitoneal paraganglioma in 52-year-old white male patient; (C) histopathological picture: Synaptophysin (++) in retroperitoneal paraganglioma in 52-year-old white male patient; (D) histopathological picture: S 100—focally positive in retroperitoneal paraganglioma in 52-year-old white male patient; and (E) histopathological picture: Ki-67 (2–3%) in retroperitoneal paraganglioma in 52-year-old white male patient.

Figure 3

(A) PET-CT scan of bilateral neck masses (carotid body tumors, CBT) in a 31-year-old white female patient with familial PPGL1 syndrome—SDHD C11X. (B) CT scan of retroperitoneal paraganglioma in a 50-year-old white male patient. (C) MRI scan of metastatic pheochromocytoma (liver metastasis) in a 73-year-old white male patient.

Figure 3

(A) PET-CT scan of bilateral neck masses (carotid body tumors, CBT) in a 31-year-old white female patient with familial PPGL1 syndrome—SDHD C11X. (B) CT scan of retroperitoneal paraganglioma in a 50-year-old white male patient. (C) MRI scan of metastatic pheochromocytoma (liver metastasis) in a 73-year-old white male patient.

Figure 4

(A) Conventional radiotherapy for bilateral CBT in a 31-year-old white female patient with familial PPGL1 syndrome—SDHD C11X. CT for treatment planning; (B) conventional radiotherapy for bilateral CBT in a 31-year-old white female patient with familial PPGL1 syndrome—SDHD C11X. Dose distribution shown on the CT scan; and (C) conventional radiotherapy for bilateral CBT in a 31-year-old white female patient with familial PPGL1 syndrome—SDHD C11X. Dose distribution shown on the CT scan.

Figure 5

(A) Stereotactic radiotherapy for metastatic pheochromocytoma (liver metastasis) in a 73-year-old white male patient. Dose distribution shown on the CT scan; (B) stereotactic radiotherapy for metastatic pheochromocytoma (liver metastasis) in a 73-year-old white male patient. Dose distribution shown on the CT scan; and (C) stereotactic radiotherapy for metastatic pheochromocytoma (liver metastasis) in a 73-year-old white male patient. Dose distribution shown on the CT scan.

Figure 6

(A) Conventional radiotherapy for retroperitoneal paraganglioma in a 52-year-old white male patient. Dose distribution shown on the CT scan; and (B) conventional radiotherapy for retroperitoneal paraganglioma in a 52-year-old white male patient. CT for treatment planning.