GSI asked Dr. J. Aidan Carney to update us regarding the syndrome of tumors now known as Carney triad, which affects young patients. Dr. Carney, a pathologist, now retired but zealously continuing his research activities into the cause of Carney Triad, is an emeritus member of the Department of Laboratory Medicine and Pathology at the Mayo Clinic in Rochester, Minnesota. His special interests during his career have included endocrine and gastrointestinal pathology, with a particular interest in syndromes.

Carney Triad Update

by J. Aidan Carney, MD, PhD, F.R.C.P.I., F.R.C.P.

1. We have read that the GISTs in Carney Triad are usually multiple tumors inside the stomach. Do Triad patients ever have a single GIST growing outward from the stomach wall, similar to adult GIST?

This situation probably occurs occasionally. A tumor protruding outwards from the stomach is less likely to cause symptoms (and therefore less likely to be recognized clinically) than one protruding into its cavity where it would be likely result in ulceration of the lining mucosa and bleeding.

2. Does the GIST in Carney Triad differ from other pediatric GISTs in any ways that are currently recognizable, or should all pediatric GIST cases be alert to the possibility of developing Triad?

Present standard pathologic examination cannot identify with certainty those patients with gastric GIST who have the triad. Therefore, all pediatric patients with gastric GISTs should be considered at risk for the triad until more is learned about them. If there was a family history of GISTs, it would be unlikely that the patient had the Carney Triad.

3. What current pathology testing is needed with each suspected Triad GIST in light of recent findings regarding family genetics, histological features, potential mutations. etc.?

The triad is not familial. Nevertheless a family history should be obtained–one never knows what new associations might be uncovered. Pathology specimens should be tested for KIT and PDGFRA mutations.

4. Is surgical resection the recommended treatment for all 3 Triad tumor types? Are any less invasive approaches possible?

In general, the gastric tumors are best treated surgically, the earlier the better, in the hope of eradicating them before they metastasize. Paragangliomas ideally should also be excised. But this may not always be possible because of the anatomical location of the tumor. In this case, embolization of the tumor may be possible. The pulmonary chondromas in the triad are benign tumors and usually do not cause symptoms. Once a diagnosis of the tumor has been established, a conservative approach should be adopted. A tumor that shows rapid growth or is causing symptoms, particularly if it is not calcified, should be biopsied to exclude metastasis from gastric GIST. Some pulmonary chondromas have been ablated using combined laser and embolization treatment.

5. What is the risk of recurrence or metastasis for Triad GISTs and paragangliomas? Please distinguish between independent new tumors and metastases. How is the outcome usually affected by the status of surgical margins?

The gastric GISTs metastasize to lymph nodes, peritoneum and liver in about one-third of the cases. In patients who have not had an initial total gastrectomy, new tumors develop in the stomach left in the patient in almost one-half of the patients. Leaving residual tumor cells in a patient (an involved margin, for example) would increase the chance of local recurrence and metastasis. The latter comment applies also to the paragangliomas.

6. In the dyad of GIST and paraganglioma, as distinct from Carney Triad, describe the differences in terms of
a) familial characteristics, and
b) proportion of males and females affected.
If a patient presented with GIST and paraganglioma, could testing identify whether this person had dyad versus triad?

The dyad in a familial disorder transmitted as an autosomal dominant trait. Experience with the disorder is very limited but probably males and females will be equally affected. As yet there is no molecular genetic test for the disorder. The important thing is to consider its possible presence and obtain a detailed family history.

7. Can Carney Triad patients have children without passing on this disorder?

Yes. No affected patient as yet has transmitted the disorder so there is a high probablity that the trait is not transmissible.

8. Recently additional tumors (adrenal cortical adenoma and esophageal leiomyoma) have been mentioned as potentially associated with the classic 3-tumor Triad. Please explain these additional components.

About 10% of patients with the triad develop non-functioning adrenal cortical adenoma(s) and 10% develop esophageal leiomyomas. Some patients develop both tumors.

9. Have tyrosine kinase inhibitor drugs such as imatinib (Gleevec) or sunitinib (Sutent) helped any Triad patients?

Generally, no. But there is always the possibility that a particular patient might benefit for unknown reasons.

10. Is research ongoing to identify the mutation that causes Carney Triad?

Yes. Reseach is going on the find the genetic causes of the Carney triad, the Carney dyad and related conditions.

11. Do other multi-component diseases bearing Dr. Carney’s name (Carney syndrome and Carney complex) have any relationship to Carney Triad? The similar names are confusing!

No. The Carney triad is the nonfamilial occurrence of gastric GIST, pulmonary chondroma and extra-adrenal paragangloma. Some patients also have adrenal cortical adenoma or esophageal leiomyoma or both. The Carney dyad is the familial occurrence of paraganglioma and gastric GIST. The Carney complex is the familial occurrence of pigmented skin spots, myxomas and adrenocortical and testicular tumors. The 3 disorders are different and not related.

12. What specialists are needed on a treatment team for Carney Triad?

The most important is a physician who is familiar with the triad and seen and treated affected patients. Depending on the circumstance he or she consult a gastroenterologist, pulmonologist or endocrinologist. Surgical consultation will depend on the tumors the patient has and their location.