Daniel M. Keller, PhD

September 26, 2013

VIENNA, Austria — One fifth of all people with a mitochondrial disorder (MID) develop a neoplasm, a new study shows. Somehow, derangements in these microscopic powerhouses of the cell confer a cancer rate 4 times higher than in the general population.

Breast cancer is the most frequent malignant neoplasm, and lipomas are the most common benign ones among patients with MIDs. Overall, women are at greater risk for any neoplasm compared with men. Up to 80% of malignant tumors in MIDs are associated with mutations in mitochondrial DNA.

"Patients with mitochondrial disorders need careful monitoring for neoplasms [so as] not to overlook them," advised Josef Finsterer, MD, PhD, from the Neurology Department at the Krankenanstalt Rudolfstiftung in Vienna, Austria, based on his retrospective evaluation of 470 patients with MIDs.

He reported the results here at the XXI World Congress of Neurology (WCN).

Frequency and Type of Neoplasms

Among the wide variety of MIDs, most affect muscle, nerve, and the central nervous system, Dr. Finsterer noted. But they are often multisystem disorders, with individual mitochondrial syndromes or nonsyndromic disorders conferring a high risk for leukemia and lymphoma, as well as solid tumors in the liver, biliary system, kidney, cervix, and pituitary and thyroid glands.

Patients with mitochondrial disorders need careful monitoring for neoplasms [so as] not to overlook them. Dr. Josef Finsterer

Although these tumor propensities have been well documented, there are few data about the frequency and type of neoplasms in MIDs. The present study assessed the frequency of benign and malignant neoplasms across a large cohort with a variety of MIDs and compared those frequencies with the frequencies in the general public.

Benign and malignant neoplasms were confirmed by histology. Modified Walker criteria were used to classify MIDs as possible, probable, or definite. Of the 470 MID cases evaluated (age range, 12 to 96 years), women outnumbered men by a ratio of 1.69:1.

Fifteen cases were definite, 54 were probable, and 401 were possible. Possible MIDs had the highest proportion of cases of both benign and malignant disease.

Table. Benign and Malignant Neoplasms in Cases of MID

Mitochondrial Disorder Group Benign Neoplasms, n (%) Malignant Neoplasms, n (%)
Definite 0 1 (6.7)
Probable 3 (5.6) 9 (16.7)
Possible 32 (8) 55 (13.7)


Dr. Finsterer counted 18 different types of malignancy in the cohort of 470 MID cases. Of the 65 malignancies seen, the 2 most common ones were in women: breast (n = 17) and cervix (n = 9). In men, prostate cancer was the most common malignancy (n = 7).

There were 9 forms of benign neoplasm, the most common being lipomas (n = 12). Some of the lipomas were quite large, occupying extensive areas of the trunk or buttocks.

Malignancies occurred twice as often in women as in men (22 men, 43 women) and tended to be at an older age (mean, 75.6 years; range, 46 to 93 years) compared with benign neoplasms (mean, 69.2 years; range, 34 to 96 years), which also occurred more frequently in women than in men with MIDs (9 men, 26 women).

Among a total population of about 8.39 million in Austria in 2012, 293,850 (3.5%) people were living with a malignant neoplasm. In contrast, of the 470 patients with MID surveyed, 65 (13.8%) had what Dr. Finsterer called a "malignoma," a 3.9-fold increased prevalence of malignancy compared with the general population.

Dr. Finsterer speculated that MIDs may be associated with an increased risk for neoplasms because of various mechanisms involving mitochondria in cell proliferation and apoptosis and as a source of oxidative stress within the cell.

Interestingly, he reported seeing no cases of lung cancer, which is normally a fairly common malignancy. He said this finding probably related to the low level of smoking among patients with MID, who already have deficits in the ability of their mitochondria to use oxygen.

More Frequent Screening

Session chair Eva Feldman, MD, PhD, professor of neurology at the University of Michigan in Ann Arbor and president of the American Neurological Association, called the findings "very interesting," as did an audience member during the question-and-answer period after Dr. Finsterer's presentation.

Dr. Feldman commented to Medscape Medical News that neurologists see many patients with MIDs, and they receive "normal cancer screening" from neurologists and internists.

However, the results of this study "would clearly indicate that women who have a mitochondrial disorder should have more frequent screening than the general population," she advised. "One would think one might want to particularly target women over the age of 65 … and increase the number of mammograms they have done."

The mix of MIDs was quite diverse, so among 65 patients with 18 different types of malignancy or 35 patients with 9 forms of benign neoplasm, Dr. Finsterer could not tell which MIDs were likely associated with which kinds of neoplasms.

"They are a broad group of disorders, but they do probably share in common the fact that mitochondria are in some way malfunctioning," Dr. Feldman said. "And in parallel, there have been a lot of discussions in cancers that there's a loss of normal mitochondrial function. So it really does make sense, and I think it really brings up some very important clinical questions."

There was no commercial funding for the study. Dr. Finsterer and Dr. Feldman have disclosed no relevant financial relationships.

XXI World Congress of Neurology (WCN). Free Papers Session 13. Presented September 23, 2013.


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