Case of spontaneous regression of carotid body tumor in a SDHD mutant: a discussion on potential mechanisms based on a review of the literature

Head and neck paragangliomas (HNPGL) are usually benign, slow-growing tumors associated with the parasympathetic nerve system. Common sites include the carotid body, the temporal bone, and the vagal body[1]. The majority of patients presents as apparently sporadic patients, whereas 10% to 20% of patients report a positive family history[2, 3]. Multiple paragangliomas may occur in up to 40% of patients[4]. In the Netherlands the majority of cases are related to mutations in the gene encoding for the oxidative chain protein succinate dehydrogenase-sub-unit-D (SDHD)[5]. In the neck, a paraganglioma presents as a non-tender mass or as a cause of lower cranial nerve palsy due to local compression. In the temporal bone, the first symptom of paragangliomas is usually pulsating tinnitus, due to the hypervascular nature of the tumor. In follow-up about 60% of the HNPGL do not exhibit growth, and if they do it typically is in an indolent growth pattern with a median tumor double time of 4.2 years[6]. Diagnosis is generally made through a combination of clinical findings and magnetic resonance imaging (MRI) studies. Treatment considerations include the nature of the tumor (malignant or benign), the location, vasculature encasement, the extent, and growth rate[6, 7]. Treatment modalities include surgery or radiotherapy/surgery; treatment of choice for carotid body tumors is surgical resection. However, because of the slow growth rate and potential treatment-related injury to the neighboring vessels and nerves, a conservative management strategy (wait-and-scan policy) should be considered[6].

In 2003 a 32-year-old female patient was referred to our institution after magnetic resonance imaging (MRI) examination in a regional hospital had revealed bilateral carotid body tumors. She had discovered a swelling in the right neck since 6 months before, and only after questioning mentioned a long-existing pulsatile tinnitus on the right side. The family history for paragangliomas was positive: her father and uncle were affected.

MRI including a gadolinium-enhanced 3D time-of-flight MR angiography sequence[8] was acquired at our institution in April 2004, and revealed hypervascular enhancing lesions in the carotid bifurcation bilaterally, consistent with carotid body tumors. The maximum transverse diameter was 23 mm on the right and 12 mm on the left (Figure1). A tympanic tumor was identified on the right side.

The right carotid body tumor was surgically resected in 2004, followed by extirpation of the tympanic tumor in 2005. No radiotherapy was applied. There were no complications from the surgical procedures. In the postoperative phase a severe obstructive sleep apnea syndrome (OSAS) was diagnosed, for which she started continuous positive airway pressure (CPAP) therapy. In 2005 she started thyroid hormone suppletion for Hashimoto disease. Between 2005 and 2008, the patient intentionally lost weight from 136 kg to 93 kg, because of a pregnancy wish which was eventually unsuccessful. During follow-up the patient regained bodyweight in 2010 to 129 kg. In 2011 she suffered anamnestically from a transient ischemic attack (with no abnormalities on imaging studies), after which she started statin treatment and therapy with carbaselate calcium and dipyridamole.

Follow-up MRI was performed with 2-year intervals (Figure2), and showed no evidence of recurrence on the operated sites. Between 2004 and 2008 there were no changes in size and enhancement pattern of the left carotid body tumor and therefore surgical resection was considered unnecessary. Unexpectedly, in 2010, the tumor was significantly smaller, and showed reduced enhancement in the center of the lesion, consistent with necrosis. Follow-up examinations in June 2011 and September 2011 showed nearly complete regression, leaving only minimal rest-abnormalities at the site of the previous tumor. Other affected family members showed no signs of regression during follow-up.

We describe a patient with hereditary bilateral head and neck paragangliomas who underwent surgical tumor removal of a right carotid body tumor and a right tympanic tumor. During the 7-year follow-up, spontaneous regression of the left carotid body tumor was noted, after an initial period without any change in tumor size. To the best of our knowledge, spontaneous involution of head and neck paragangliomas has not been reported before. In our referral center for paragangliomas, the present case with spontaneous involution represents the first from an estimated total of more than 400 followed cases.

Spontaneous regression of tumors in general is a rare phenomenon, although numerous cases and case series can be found in the literature. Spontaneous remission of tumors with a common neural crest embryological origin as paragangliomas has been described as well. Regression of pheochromocytomas after initial presentation with hypertensive crises or shock has been reported[9‐11], as well as spontaneous regression[12], Another known entity is spontaneous regression in a subset of pediatric neuroblastomas, especially those detected with mass screening and with biologically favorable characteristics[13, 14].

In conclusion, the present case underlines the indolent growth pattern of head and neck paragangliomas and for the first time describes a rare manifestation of involution of a carotid body tumor.

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.