Author + information
- Alessandra Serio, MD, PhD,
- Valentina Favalli, PhD,
- Lorenzo Giuliani, MSc,
- Nupoor Narula, MD,
- Maurizia Grasso, BD, PhD,
- Riccardo G. Borroni, MD, PhD,
- Jérôme Bertherat, MD, PhD,
- Bernard Peissel, MD,
- Siranoush Manoukian, MD and
- Eloisa Arbustini, MD∗ ()
- ↵∗Centre for Inherited Cardiovascular Diseases, IRCCS Foundation University Hospital Policlinico San Matteo, Piazzale Golgi, 19, 27100 Pavia, Italy
Cardio-oncology is an important, expanding discipline. Although most developing programs address the cardiotoxicity of old and novel anticancer drugs, cardio-oncology expertise and experience are also needed for rare multiorgan diseases, which require interdisciplinary evaluation to provide optimal, timely care for patients and families. Carney complex type I is the paradigmatic example that cardiologists should consider when diagnosing cardiac myxoma and oncologists should consider when diagnosing endocrine, cutaneous, and neural myxomatous neoplasms, especially in patients demonstrating pigmented lesions of the skin and mucosae (1). The disease was first described as a “complex including myxomas, spotting pigmentation and endocrine over-reactivity” (Carney Complex 1 [CNC1], OMIM #160980). The diagnosis is made by the presence of 2 major criteria confirmed by histology, imaging, or biochemical testing, or 1 major and 1 supplemental criterion (2). The disease gene is protein kinase cyclic adenosine monophosphate–dependent regulatory type I alpha (PRKAR1A) that maps at the 17q24.3 locus (3); genetic testing confirms the clinical diagnosis in probands and provides early diagnosis in younger relatives.
In the previous scenario, we observed a family (Figure 1A) with autosomal-dominant cardiac myxoma, breast cancer and pigmented cutaneous lesions. The proband’s mother (II:4) was reported as having dextroposition of the aorta, metachronous breast cancer (at 55 and 74 years of age), hepatic cysts, dolichosigma, and thalassemia trait; she had 2 surgeries for left atrial myxoma at 64 and 67 years of age. The proband (III:3) herself is a 50-year-old female with a long clinical history, since 32 years of age, of breast myxoid fibroadenomas, intraductal papillomas, and intraductal carcinoma ending in left mastectomy at 43 years of age and right mastectomy at 48 years of age. In the midst, she also developed a melanoma. In 2015, echocardiographic study demonstrated presence of a left atrial myxoma (Figure 1B). Her daughter (IV:1) underwent her first cardiologic evaluation at 8 years of age: echocardiography demonstrated presence of an atrial myxoma (Figure 1B). The girl had lentigo of the lips (Figure 1A). The genetic defect identified in the family (PRKAR1A c. 761_762delTC p. Ser 254Tyr fsx15) predicts a truncated protein, and was identified in the proband and her daughter and in the affected mother. The proband’s sister tested negative for the mutation (III:2).
This typical example of Carney syndrome highlights the multidisciplinary diagnostic work-up in patients with myxoma (cardiology perspective), extracardiac myxomatous neoplasms (oncology perspective), and melanoma (dermatology perspective). In syndromes affecting more than 1 organ, the first clinical episode can fall within either specialty. Therefore, all specialists exploring traits pertinent to this syndrome should include Carney complex in the list of differential diagnoses. The only differential diagnosis for cardiac myxoma is the “isolated” or “sporadic myxoma,” whereas the differential diagnosis of noncardiac traits is more complex and should include all syndromes with lentigines and tumors similar to those that recur in Carney complex, reviewed in Kirschner et al. (3). The precise diagnosis can save a life, especially when complex syndromes include the risk of malignancies and helps management. The youngest member of the family (IV:1) is affected by myxoma and melanocytic skin lesions: the myxoma shows a large implant and smooth borders, encouraging careful monitoring rather than early surgery, given that future surgeries, both cardiac and noncardiac, are expected to be needed in the course of her life. In fact, cardiac myxomas tend to recur in Carney complex (4). Similarly, the high risk of developing malignancies calls for personalized clinical monitoring and need for close longitudinal follow-up. Up to 10% of cardiac myxomas occur in Carney syndromes (4). The number of missed diagnoses is likely high. Cardiologists and cardiac surgeons caring for these patients should be encouraged to organize multidisciplinary evaluation. We suggest that Carney complex should be excluded in all patients presenting with cardiac myxomas.
Please note: Dr. Bertherat has served as a board member for Novartis, HRA, and Shire. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Renu Virmani, MD, served as Guest Editor for this article.
- American College of Cardiology Foundation