Atrial myxoma and associated Cushing syndrome: Carney complex.

A 33-year-old woman with a history of high blood pressure since she was 8 years old, hypothyroidism, polycystic ovary syndrome, metabolic syndrome, multiple nevi, and a maternal family history of death at age 50 due to malignant high blood pressure and heart failure. Cushing's syndrome secondary to a secretory pituitary microadenoma was diagnosed, being the cause of secondary arterial hypertension, and ruling out other causes such as renal stenosis and coarctation of the aorta. A transthoracic and transesophageal echocardiogram was performed, which detected a left atrial myxoma. Given the presence of an atrial myxoma, Cushing's syndrome and polycystic ovary syndrome, a diagnosis of Carney Complex was made due to the presence of positive Stratakis criteria. The cardiac tumor was resected, and pathology confirmed that it was an atrial myxoma. She evolved clinically stable in outpatient controls in a 6-month follow-up. Resection of the pituitary microadenoma is planned as a curative treatment for Cushing's syndrome and arterial hypertension.

Mujer de 33 años, con antecedentes de hipertensión arterial desde los 8 años, hipotiroidismo, síndrome de ovario poliquístico, síndrome metabólico, nevos múltiples y antecedente familiar materno de muerte a los 50 años por hipertensión arterial maligna e insuficiencia cardiaca. Se diagnosticó síndrome de Cushing secundario a un microadenoma hipofisario secretor, siendo la causa de la hipertensión arterial secundaria, y descartándose otras causas como estenosis renal y coartación de aorta. Se realizó u n ecocardiograma transtorácico y transesofágico que detectaron un mixoma auricular izquierdo. Ante la presencia de un mixoma auricular, síndrome de Cushing y síndrome de ovario poliquístico se llegó al diagnóstico de Complejo de Carney por la presencia de criterios de Stratakis positivos. Se realizó la resección del tumor cardiaco, y la anatomía patológica confirmó que se trataba de un mixoma auricular. Evolucionó clínicamente estable en controles ambulatorios en un seguimiento de 6 meses, y se planifica la resección del microadenoma hipofisario como tratamiento curativo del síndrome de Cushing y la hipertensión arterial.

A case report and literature review of Carney complex with atrial adenomyxoma.

BACKGROUND: Carney complex (CNC) is a rare multiple endocrine neoplasia syndrome characterized by mucocutaneous lentigines/ blue nevi, cardiac myxoma and endocrine overactivity. Here, we report a CNC case with PRKAR1A gene mutation characterized by left atrial adenomyxoma to explore the diagnosis and treatment of CNC. CASE PRESENTATION: A 42-year-old woman with a history of cardiac tumour surgery presented with typical features of Cushing syndrome, including central obesity, buffalo hump, mild facial plethora, purple striae on the lower abdomen, and spotty skin pigmentation. Left atrial adenomyxoma and thyroid papillary carcinoma were identified by postoperative histologic assays. Genetic screening revealed a pathogenic germline heterozygous mutation of c.682C > T (p.R228X) in exon 7 of the PRKAR1A gene. The clinical features and normal ACTH levels suggest this patient suffered the ACTH-independent primary pigmented nodular adrenocortical disease (PPNAD) with cyclic hypercortisolism or ACTH-dependent Cushing syndrome. CONCLUSION: CNC is uncommon, however, if a patient develops clinical features involving multiple endocrine and non-endocrine tumors, especially Cushing syndrome and cardiac myxoma, CNC should be considered. Genetic analysis is recommended in patients with suspected CNC.

Bilateral tympanic myxoma: A CARE case report.

INTRODUCTION: Ear myxoma is a rare benign tumor sometimes located on the pinna and the external auditory meatus, associated with Carney Complex (CNC). However, tympanic membrane myxoma has never been described. We present here a case of bilateral tympanic membrane myxoma, following CARE guidelines. OBSERVATION: A 35-year-old woman presented to our department with right otalgia. Otoscopy showed non-specific bilateral tissular masses in the posterior quadrant of the tympanic membranes, with normal hearing thresholds. CT-scan showed a tissular mass without osteolysis. Right-side resection confirmed the lesion as being a myxoma, ruling out differential diagnoses. The patient was then screened for extra-otologic lesions typically associated with ear myxoma in CNC. Only perilabial lesions similar to lentigos suggested CNC. Cardiac, endocrine and thyroid assessment were normal. Genetic testing for a PKRAR1A gene mutation was negative. DISCUSSION: This is to our knowledge the first reported case of tympanic membrane myxoma. It is of particular interest, being bilateral and showing spontaneous involution of the left lesion over the years. Genetic screening was negative; nevertheless, thorough evaluation is essential due to the life-threatening nature of cardiac myxoma and the frequently associated malignant tumors. Potential new mutations associated with CNC should be considered in the future.

A Novel Missense PRKAR1A Variant Causes Carney Complex.

The Carney complex (CNC) is an autosomal dominant disorder characterized by endocrine and nonendocrine tumors. Loss-of-function variants of protein kinase A regulatory subunit 1 alpha (PRKAR1A) are common causes of CNC. Here, we present the case of a patient with CNC with a novel PRKAR1A missense variant. A 21-year-old woman was diagnosed with CNC secondary to acromegaly and adrenal Cushing syndrome. Genetic analysis revealed a novel missense heterozygous variant of PRKAR1A (c.176A>T). Her relatives, suspected of having CNC, also carried the same variant. RNA analysis revealed that this variant led to nonsense-mediated mRNA decay. In vitro functional analysis of the variant confirmed its role in increasing protein kinase A activity and cyclic adenosine monophosphate levels. This study broadens our understanding of the genetic spectrum of CNC. We suggest that PRKAR1A genetic testing and counseling be recommended for patients with CNC and their families.

Carney complex syndrome manifesting as cardioembolic stroke: a case report and review of the literature.

BACKGROUND: "Carney Complex (CNC) is a familial lentiginosis syndrome, caused by PRKAR1A mutations that lead to cyclic AMP-dependent protein kinase (PKA) signaling pathway abnormalities, predisposing to a variety of skin tumors, myxomas and endocrine tumors. METHODS/RESULTS: We describe a Greek family diagnosed with CNC after recurrent embolic strokes, secondary to left-sided atrial myxomas. There are limited cases in the literature describing this type of presentation for CNC; typically, most cases present with an endocrine syndrome. Our case serves as a reminder of this rare, underdiagnosed syndrome and its wide phenotypic spectrum. It is followed by a review of the current literature on cases with cerebrovascular disease as a manifestation of CNC. CONCLUSION: The co-occurrence of emboligenic cardiac myxomas and skin lesions should be an indication for screening for CNC.

Carney complex: left atrial myxoma in a patient with past pituitary microadenoma and lentiginosis.

The Carney complex (CNC) is a rare autosomal dominant genetic complex that is characterised by multiple neoplasms consisting of neuroendocrine and cardiac tumours, with only 750 cases reported worldwide as of 2017. Cardiac tumours, in the context of the CNC, are of unique importance since the leading causes of death in patients with CNC are cardiac. To prevent sudden cardiac death and embolic events, a difficult diagnosis must be made and postdiagnostic screenings must be regular. We present a case of a 52-year-old man, with a medical history of pituitary microadenoma and facial lentiginosis, who presented with dyspnoea 2 months after suffering a cerebrovascular accident.

Cardiac myxoma misdiagnosed as infective endocarditis: a case of Carney complex.

BACKGROUND: Infective endocarditis and cardiac myxoma have common features including fever, systemic embolism and intra-cardiac masses. For this reason, these diseases are often misdiagnosed one for another despite proper imaging studies. Herein, we report a case of suspected infective endocarditis in a patient with acute stroke, fever and a mass adjacent to the mitral valve. CASE PRESENTATION: A 24-year-old male patient presented with recurrent fever and stroke. In view of a history of Cushing syndrome and a mobile mass in the left atrium, infective endocarditis was highly suspected. He was transferred for emergency cardiac surgical intervention. During surgery, intraoperative transesophageal echocardiography revealed a 7 cm mass attached to the interatrial septum. The mass was excised through right mini-thoracotomy and pathological examination confirmed the presence of a myxoma. Based on the above clinical findings and genetic analysis, the diagnosis of Carney complex was confirmed. CONCLUSIONS: Infective endocarditis and cardiac myxoma have common features and can be misdiagnosed. If a young patient presenting with embolic stroke had a history of an endocrine neoplasm, Carney complex should be considered in the differential diagnosis of infective endocarditis.

Primary pigmented meningeal melanocytoma originating in Meckel cave in a patient with carney complex: A case report.

RATIONALE: Primary melanin-producing tumors are rare extra-axial neoplasms OPEN of the central nervous system. In the literature, few case reports have discussed neoplasms involving the cavernous sinus; of these, only 4 have reported on neoplasms originating in Meckel cave. The diagnostic approach, including clinical and radiological analysis, is challenging, and cytopathological assessment with a molecular basis is the best approach to discriminate between these lesions. Herein, we discuss the pathophysiology, diagnostic approach, intraoperative features, and postoperative management in a unique case of primary pigmented meningeal melanocytoma originating in Meckel cave in a patient who was diagnosed with Carney complex (CCx) and sickle cell disease (SCD). PATIENT CONCERNS: A 23-year-old man diagnosed with SCD had also been diagnosed previously with CCx, without any familial history or neurocutaneous melanosis. He had experienced headaches accompanied by left facial pain and paresthesia for 2 months. DIAGNOSIS: The initial computed tomography scan and magnetic resonance imaging (MRI) revealed a mass arising from the left Meckel cave. On MRI, it followed the signal intensity of melanin. He underwent subtotal resection of the mass. Considering the patient's history of CCx, melanocytic schwannoma was the most relevant diagnosis. A postoperative histopathological examination was suggestive of benign pigmented meningeal melanocytoma. INTERVENTIONS: The patient underwent an uneventful subtotal resection of the mass through a left temporal linear incision. OUTCOMES: The patient showed progressive improvement of neurologic deficits, and after 2 years of follow-up, he did not present with any new complaints. LESSONS: To the best of our knowledge, this is the first report of the unusual presentation of both SCD, as well as of primary pigmented meningeal melanocytoma in a patient with CCx. Complete surgical resection can be curative in most cases of melanocytoma. The presence of CCx with SCD suggests potential shared genetic contributions that will require further exploration.

An Unusual Presentation of Carney Complex

Carney complex (CNC) is a multiple neoplasia syndrome, characterized by pigmented lesions of the skin and mucosa, cardiac, cutaneous and other myxomas and multiple endocrine and non-endocrine tumors. Most of the cases have an inactivating mutation in the PRKAR1A gene. Osteochondromyxoma (OMX) is an extremely rare myxomatous tumor of bone, affecting 1% of CNC patients. Large cell calcifying Sertoli cell tumor (LCCSCT) is a testicular tumor affecting more than 75% of males with CNC. Here, we report an atypical case of CNC without typical pigmented skin lesions, presenting with a bone based tumor as the first manifestation. Initial presentation was for a recurrent, locally invasive intranasal tumor without definite diagnosis. Further clinical developments during follow up, central precocious puberty and testicular tumor with calcification, led to the diagnosis of LCCSCT, a CNC-related tumor. Histopathologic examination of the intranasal tumor was re-evaluated with this knowledge and OMX was diagnosed. Coexistence of OMX and LCCSCT suggested CNC. Genetic analysis revealed a heterozygous non-sense p.Trp 224* (c.672G>A) in the PRKAR1A gene. In our case, the diagnosis of OMX was delayed, because it is extremely rare and little is known about this tumor. Thus the aim of this report was to alert other clinicians to consider CNC if OMX is diagnosed.

Pituitary apoplexy after cardiac surgery in a 14-year-old girl with Carney complex: a case report.

A 14-year-old girl was referred to our department because of headache and visual impairment following the resection of recurrent cardiac myxoma. Head magnetic resonance imaging (MRI) scan detected an intra- and supra-sellar tumor. Moreover, the patient showed the presence of spotty skin pigmentations on her cheeks and lower lip. Blood examination revealed hypothyrotropinemia, and ultrasonography results revealed multiple thyroid nodules. She was diagnosed with Carney complex (CNC). Her pituitary tumor was suspected as growth hormone (GH)-secreting adenoma, because overgrowth was observed in the patient. However, biochemical examinations, including oral glucose tolerance test, failed to show the characteristic findings of GH-secreting adenoma. In contrast, insulin tolerance test showed GH deficiency. Her visual impairment improved without performing decompression surgery, and the tumor size decreased, as per the MRI findings. Based on clinical course, the patient was diagnosed with pituitary apoplexy in pituitary adenoma, following which she was discharged. At 3 months after discharge, thyrotropin-releasing hormone loading test performed revealed low thyrotropin-stimulating hormone and thyroid hormone levels, and the patient was in a depressed mood. Therefore, l-T4 replacement was initiated, following which her GH secretory capacity gradually improved. Here, we report, to the best of our knowledge, the first case of a patient with pituitary apoplexy in CNC. Such condition must be identified in young patients with recurrent cardiac myxoma, and examinations, such as head MRI, must be performed.

Non-syndromic aortic valve myxoma in a teen, cause of angina symptoms.

BACKGROUND: Cardiac myxoma, a common benign primary tumor of the heart can be categorized into syndromic (Carney Complex) and non-syndromic(isolated). Carney Complex associated myxomas can be found in any region and system (cardiac, cutaneous, osseous, genitalia), and may manifest at a tender age. On the contrary, non-syndromic cardiac myxomas are usually confined to the chambers, and symptoms often present from 5th decade of life. Aortic valve myxoma is a very unusual occurrence, and presentation in a teen is extremely rare. CASE REPORT: We share a case of aortic valve myxoma, uncovered using echocardiography in a 16-year-old male, admitted with complaints of exertional chest pain, dyspnoea and systolic murmur. Patient underwent uneventful surgery for tumor excision, and discharged 6-days post operation. CONCLUSION: Given the high risk of developing cardiogenic stroke, infective endocarditis, degenerative effects on aortic valve leaflets and possible sudden death, like many other centers, we advocate for immediate liquidation of aortic myxoma regardless of age and symptoms.

Distinct Genomic Patterns in Pigmented Epithelioid Melanocytoma: A Molecular and Histologic Analysis of 16 Cases.

Pigmented epithelioid melanocytoma (PEM) is considered an intermediate grade melanocytic lesion that is histologically indistinguishable from epithelioid blue nevi associated with Carney complex. PEM are characterized by an intradermal population of heavily pigmented epithelioid-shaped melanocytes along with some spindled and dendritic melanocytes with frequent melanophages. These melanocytic tumors occasionally involve regional lymph nodes but only rarely result in distant metastases. Recent studies have demonstrated a variable but limited number of specific genomic aberrations including protein kinase A regulatory subunit alpha (PRKAR1A), BRAF, GNAQ, and MAP2K1 mutations as well as protein kinase C alpha isoform (PRKCA) fusions. We performed an 8-year retrospective review of our database and identified 16 cases of PEM. Using targeted DNA sequencing and RNA-seq to assess 1714 cancer-related genes, we detected gene fusions involving PRKCA in 31% of cases (5/16) with 5' partners SCARB1(12q24) in 2 cases, CD63 (12q13) in 1 case, ATP2B4 (1q32) in 1 case, and MAP3K3 (17q23) in 1 case. Additional fusions were identified in TPR-NTRK1 (1/16), ALK (1/16), and MYO5A-NTRK3 (1/16). PRKCA fusion lesions tended to occur in younger-aged patients and histologic examination demonstrated sheets of monomorphic epithelioid-shaped melanocytes, moderate to high-grade nuclear atypia, and higher mitotic activity (P=0.037). Our gene panel also identified previously described mutations in PRKAR1A, GNAQ, MAP2K1, BRAF, NF1. To our knowledge, this is the largest and most comprehensive study of PEM integrating molecular data with histologic features that can be utilized in future studies for improved subclassification and prognostication of heavily pigmented melanocytic neoplasms.

Carney Complex.

Carney complex is a rare, autosomal dominant, multiple endocrine neoplasia and lentiginosis syndrome, caused in most patients by defects in the PRKAR1A gene, which encodes the regulatory subunit type 1α of protein kinase A. Inactivating defects of PRKAR1A lead to aberrant cyclic-AMP-protein kinase A signaling. Patients may develop multiple skin abnormalities and a variety of endocrine and non-endocrine tumors. Endocrine manifestations include primary pigmented nodular adrenocortical disease, that may cause Cushing syndrome, growth-hormone secreting pituitary adenoma or pituitary somatotropic hyperplasia which can result in acromegaly, as well as gonadal and thyroid tumors. Non-endocrine tumors associated with Carney complex include myxomas of the heart, breast, and other sites, psamommatous melanotic schwannomas, breast ductal adenomas, osteochondromyxomas, and a predisposition to a number of malignancies from adrenal to pancreatic and liver cancer.

Carney Syndrome Presented as a Pathological Spine Fracture in a 35-Year-Old Male.

BACKGROUND Carney complex (CNC) is a genetic disorder that presents as an adrenocorticotropic hormone (ACTH)-independent variant of endogenous Cushing syndrome. It was first reported in 1985 and was described as a form of multiple endocrine hyperplasia associated with mutations of the c-AMP-dependent protein kinase (PRKAR1A) gene that causes bilateral adrenal hyperplasia. We report a case of an incidentally found CNC in a 35-year-old male, and this case report focuses on the diagnostic scheme as well as the surgical treatment of this rare challenging condition. CASE REPORT A-35-year-old male presented with pathological thoracic spine fracture. The patient exhibited obesity, facial flushing, red-purplish streaks on the abdominal wall, multiple pigmented nevi of the trunk, and hypertension. Family history was positive for cardiac myxoma. Laboratory investigation showed ACTH-independent Cushing syndrome. Abdominal magnetic resonance imaging and computed tomography scan showed bilateral adrenal hyperplasia. The ensuing Liddle test revealed the characteristic paradox increase of 24-hours urine cortisol for CNC. After a bilateral retroperitoneoscopic adrenalectomy, histologic examination confirmed the presence of bilateral primary pigmented nodular adrenocortical disease (PPNAD). Genetic testing revealed a unique mutation of the responsible PRKAR1A gene. CONCLUSIONS CNC presence was suspected due to the family history. Its characteristic pathologic manifestation called PPNAD, clinically presents as an ACTH-independent Cushing syndrome with paradoxical positive response of urinary glucocorticosteroid excretion after dexamethasone administration (Liddle's test). Bilateral retroperitoneoscopic adrenalectomy constitutes an acceptable surgical option for PPNAD.

Embolic stroke, left atrial myxoma and gigantism in a patient with Carney complex with additional features suggestive of Marfan syndrome.

A 16-year-old boy presented to the emergency department with a sudden weakness on the right side of the body and was diagnosed as having embolic stroke. Later on, the patient was diagnosed as having Carney complex (CNC). The neurological complication might be caused by left atrial myxoma as a feature of CNC. Surprisingly, the patient showed some additional features such as positive wrist and thumb signs, pectus carinatum deformity and plain flat feet, suggestive of Marfan syndrome. This case demonstrated that both of these syndromes might coexist in the same patient, suggesting that proper diagnostic and management were key factors that affected prognosis. He showed an improved condition after he had received medical treatments, undergone tumour excision and physiotherapy. Further evaluation was needed to improve patient outcomes.

[Asymptomatic Cardiac Myxoma Complicated with Carney Complex;Report of a Case].

Carney complex(CNC) is a rare genetic syndrome, characterized by spotty pigmentation of the skin, cardiac myxomas and multiple endocrine tumors. We present a case of asymptomatic cardiac myxoma associated with CNC. She was 49 year-old healthy woman whose son was known to have CNC. She was also diagnosed as CNC due to her family history, typical cutaneous findings and screening endocrine test. Screening ultrasound echocardiography resulted in discovering her asymptomatic left atrial myxoma of 30 mm size. Tumor was successfully resected via median sternotomy and no signs of recurrence were observed at 1 year follow up. Periodical follow up is mandatory because of its high recurrence rate.