Compared to sporadically occurring paragangliomas and pheochromocytomas (PGL/PHEO) the tumors associated with an SDHx mutation occur at an earlier point in time, are usually found in multiple locations, develop on both sides, and tend to recur. Benign paragangliomas and pheochromocytomas generally grow slowly, while malignant tumors are typically more aggressive.
The greatest risk of cancer is associated with mutations in the SDHB gene. Patients with this genetic alteration exhibit higher rates of mortality and have paragangliomas with a much stronger tendency to spread (metastasize) than patients with other SDH mutations.
Paragangliomas in these regions are typically associated with the parasympathetic nervous system, which – along with the sympathetic nervous system – is part of the involuntary nervous system. These paragangliomas generally do not secrete hormones. Clinical symptoms are usually caused by the space-occupying growth of these tumors, since these types of tumors do not tend to spread (metastasize).
Different symptoms can occur depending on the location.
In the area of the carotid artery (carotid bifurcation tumors), these paragangliomas are usually asymptomatic unilateral space-occupying lesions, which only lead to complaints – such as sensation disorders or motor impairments in the neck, jaw, and facial regions – until the tumor grows larger.
Tumors located in the vagus nerve region (the tenth cranial nerve, which has a large number of motor and sensory properties) manifest the same way as the carotid bifurcation tumors described above. In addition, symptoms such as hoarseness, a foreign body sensation in the throat, swallowing disorders, pain, coughing, and aspiration (penetration of fluid or food into the airways) may occur.
Paragangliomas in the area of the ear may trigger tinnitus or loss of hearing.
Paragangliomas in these regions are typically associated with the sympathetic nervous system, which – along with the parasympathetic nervous system – is part of the involuntary nervous system. Tumors in these regions usually exhibit excessive hormone production (e.g. adrenaline and/or noradrenaline).
Pheochromocytomas are tumors that usually occur in the adrenal medulla and produce hormones such as adrenaline and noradrenaline (catecholamines). However, they can also occur outside of the adrenal glands, where they are called sympathetic paragangliomas. This type of tumor, when associated with HPP, manifests the same way as tumors that occur sporadically. They are usually discovered because of one of the following scenarios:
Sympathetic paragangliomas outside of the adrenal glands have an increased tendency towards malignant transformation. This tendency is much lower with pheochromocytomas.
These are malignant connective tissue tumors of the gastrointestinal tract – usually located in the stomach when associated with HPP. Stomach bleeding may occur as a complication. While these tumors can occur with mutations in all of the SDH genes, it is most common with mutations in the SDHA gene.
These tumors have been associated with SDHB and SDHD mutations.