Possible Genetic Cause of Head, Neck Tumors Common among Family Members Identified

Website: http://www.sic2004.org/

Newswise — Researchers have identified a region of genetic alteration and pattern of inheritance in genes responsible for paragangliomas (glomus tumors) of the head and neck that are genetically linked among family members. This discovery may lead to testing for early detection of these tumors and better treatment outcomes. The same study indicates that pre-operative embolization, a procedure that blocks blood flow to a tumor, makes surgery to remove the tumor safer by reducing blood loss, surgical time, and complications. A paraganglioma of the head and neck is also known as a glomus tumor, an often benign growth that develops slowly (these tumors are rarely malignant). These tumors are often diagnosed at later stages due to their lack of significant symptoms early on. It is well known that genetic inheritance is a risk factor for paragangliomas, but the specific genetic alteration that conveys this risk or its inheritance pattern have not yet been identified.

Treatment for paraganglioma usually involves surgical removal (resection), which can be difficult because the tumors typically have a large blood supply by the time they are diagnosed. Developing surgical methods that reduce blood loss is important because blood loss during surgery can affect patient outcome. Embolization is a procedure that blocks the blood vessels of a tumor, reducing or eliminating blood flow and diminishing the size of the tumor. Done pre-operatively, the procedure can reduce blood loss during surgery and overall surgical time.

This study was designed to determine the inheritance pattern and potential genetic alteration responsible for familial paragangliomas of the head and neck and to examine the use of pre-operative embolization during surgical treatment. The author of the study, "Genetic and Clinical Evaluation of Familial Paragangliomas of Head and Neck" is Sukamal Saha, MD, FACS, FRCS, of the Advanced General & Oncological Surgery Associates, Flint, MI. His findings will be presented at the 6th International Conference on Head and Neck Cancer (http://www.sic2004.org) being held August 7-11, 2004, at the Wardman Park Marriott in Washington, DC.

Methodology: Seventeen patients with paragangliomas of the head and neck were studied (age range, 28-82 years), including eight cases of familial paragangliomas with 34 asymptomatic family members, and nine cases of non-familial paragangliomas. All patients were clinically evaluated, received a computed tomography scan and magnetic resonance imaging of head and neck, and selective carotid artery angiogram. Preoperative embolization and resection within 24 hours was performed on 11 patients. Blood samples for genetic analysis were taken from all the patients and asymptomatic family members.

Results: Genetic analysis revealed that a deletion of the P1 or P2 promotor regions occurred in six patients with familial paragangliomas and seven familial asymptomatic patients. Further analysis showed that this deletion was transferred to the children through male relatives.

Those patients who underwent preoperative embolization had an average blood loss of 125 mls and an operation time of 1.5-3.5 hours compared to an average of 800-4,000 mls blood loss and 3.5-8 hours of operation time for patients without the procedure. The few complications included one patient developing transient palsy of the cranial nerve VII, one patient developing Horner's syndrome, and three patients developing mild hoarseness and dysphagia (difficulty swallowing).

Conclusion: This study's genetic analysis indicates that a screening for familial paraganglioma can be done by a blood test to detect deletion of the P1 or P2 promotor region. Detection of the tumor or identification of those at risk for the tumor can lead to better treatment without development of major symptoms. Genetic analysis also detected a paternal transmission of the gene alteration in a pattern suggestive of an autosomal dominant mode of inheritance.

Preoperative embolization of paragangliomas and a timely resection within 24 hours can considerably reduce blood loss, complications, and surgical time in select cases, a finding that confirms earlier study results. The authors suggest that pre-operative embolization should be a new standard of care for select patient groups.