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.

Recurrent multi-cameral cardiac myxomas in a child with Carney complex.

Cardiac myxoma is a relatively rare tumour, usually solitary, that occurs primarily in the left atrium of adults, but comprises only 30% of cardiac tumours in children. We recently treated a 12-year-old girl with multiple recurrent myxomas in three cardiac chambers(following surgical resection 3 years earlier). Genomic analysis showed the PKAR1A mutation typical for Carney complex.

Ultrasonographic features of cutaneous myxomas in a patient with Carney complex

Abstract Carney complex is a rare genodermatosis characterized by cardiac and cutaneous myxomas, among other tumors. In the majority of cases, cutaneous myxomas precede the diagnosis of cardiac myxomas, which are the main cause of death in these patients. Despite the fact that the diagnosis of cutaneous myxomas is histopathological, high-frequency ultrasonography plays an essential role in the differential diagnosis with other cutaneous and subcutaneous tumors. The authors of the present study describe, for the first time in the literature, the ultrasonographic features of both variants of cutaneous myxomas, superficial and subcutaneous, in a patient with a Carney complex.

Ultrasonographic features of cutaneous myxomas in a patient with Carney complex.

Carney complex is a rare genodermatosis characterized by cardiac and cutaneous myxomas, among other tumors. In the majority of cases, cutaneous myxomas precede the diagnosis of cardiac myxomas, which are the main cause of death in these patients. Despite the fact that the diagnosis of cutaneous myxomas is histopathological, high-frequency ultrasonography plays an essential role in the differential diagnosis with other cutaneous and subcutaneous tumors. The authors of the present study describe, for the first time in the literature, the ultrasonographic features of both variants of cutaneous myxomas, superficial and subcutaneous, in a patient with a Carney complex.

A novel mutation in PRKAR1A gene in a patient with Carney complex presenting with pituitary macroadenoma, acromegaly, Cushing's syndrome and recurrent atrial myxoma

SUMMARY Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.

A novel mutation in PRKAR1A gene in a patient with Carney complex presenting with pituitary macroadenoma, acromegaly, Cushing's syndrome and recurrent atrial myxoma.

Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.

Palatal Soft Tissue Myxoma in a Patient with Carney Complex.

Carney complex (CNC) is a rare, autosomal dominant multiple neoplasia syndrome. Although cutaneous myxomas commonly occur in CNC patients, intraoral myxomas are extremely rare. We present a case of a palatal myxoma in a 21-year-old female patient with CNC, along with a review of the pertinent literature. She presented with a sessile nodule on the hard palate that microscopically showed a multilobulated and highly vascularized myxomatous tissue composed of loosely-arranged spindle, polygonal, and stellate cells, suggestive of myxoid neurofibroma. Six years after the oral lesion was removed, she presented with a growth hormone (GH)-producing pituitary adenoma, a cardiac myxoma, two cutaneous myxomas on the lower abdomen area, and one myxoma in the vaginal mucosa. Therefore, the final diagnosis of the palatal lesion was of a soft tissue myxoma related to CNC. The patient remains on close follow-up, with no recurrences of the palatal myxoma after 7 years.

Genetic Mutations and Variants in the Susceptibility of Familial Non-Medullary Thyroid Cancer.

Thyroid cancer is the most frequent endocrine malignancy with the majority of cases derived from thyroid follicular cells and caused by sporadic mutations. However, when at least two or more first degree relatives present thyroid cancer, it is classified as familial non-medullary thyroid cancer (FNMTC) that may comprise 3-9% of all thyroid cancer. In this context, 5% of FNMTC are related to hereditary syndromes such as Cowden and Werner Syndromes, displaying specific genetic predisposition factors. On the other hand, the other 95% of cases are classified as non-syndromic FNMTC. Over the last 20 years, several candidate genes emerged in different studies of families worldwide. Nevertheless, the identification of a prevalent polymorphism or germinative mutation has not progressed in FNMTC. In this work, an overview of genetic alteration related to syndromic and non-syndromic FNMTC is presented.

MINOCA por mixoma atrial esquerdo: relato de caso / Left atrial myxoma MINOCA: case report

INTRODUÇÃO: O termo MINOCA (Myocardial Infarction with Nonobstrutive Coronary Arteries) é utilizado para se referir aos casos de infarto agudo do miocárdio (IAM) em que na angiografia as artérias coronárias são normais. A MINOCA representa 14% de todas as causas de IAM, sendo mais frequente em mulheres jovens. Os mixomas são os tumores benignos primários do coração mais frequentes (40-50%). RELATO DE CASO: VMF, 49 anos, sexo feminino, apresentando dispneia aos esforços há 4 meses. O eletrocardiograma evidenciou área eletricamente inativa anterior extensa (figura 1) e o ecocardiograma (figura 2), fração de ejeção de ventrículo esquerdo (VE) de 55% (método Simpson), acinesia do ápice e dos segmentos apicais de todas as paredes e presença de imagem sugestiva de massa homogênea, com contornos regulares, localizada no interior do átrio esquerdo, medindo 25x28mm. Foi submetida à ressecção tumoral, com anatomopatológico confirmando mixoma atrial esquerdo. Paciente manteve seguimento ambulatorial, onde realizou angiotomografia de coronárias com escore de cálcio de zero, sem placas ateroscleróticas ou redução luminal. A ressonância magnética cardíaca (RMC), figura 3, mostrou fibrose miocárdica difusa, transmural, poupando apenas os segmentos anterolateral e inferolateral basais, com áreas de fibrose microvascular. A paciente evoluiu com disfunção ventricular, recebendo o tratamento medicamentoso recomendado. DISCUSSÃO: O diagnóstico de MINOCA na evolução deste caso pode ser bem estabelecido pelas alterações eletrocardiográficas, ecocardiográficas e, principalmente pelas alterações da RMC com a comprovação de realce tardio transmural de padrão coronariano. Foram afastadas lesões coronárias estruturais pela angiotomografia coronária. A presença de massa tumoral atrial esquerda levanta a possibilidade de embolização coronária, seja por fragmentos da massa ou por trombos formados pela sua presença, ou ainda por estado de hipercoagulabilidade induzida pelo tumor. A presença de embolização sistêmica em portadores de mixoma de átrio esquerdo é bem conhecida, embora o diagnóstico de embolia coronária seja extremamente rara. CONCLUSÃO: Massas tumorais cardíacas devem ser lembradas diante de casos de MINOCA, e um ecocardiograma e RMC são métodos diagnósticos importantes para confirmação deste diagnóstico. O tratamento cirúrgico precoce e possivelmente anticoagulação devem ser considerados para prevenção desta ocorrência

Mixoma cardíaco: reporte de caso / Cardiac Myxoma: Case Report

Los tumores cardiacos se pueden dividir en primarios y secundarios. Aproximadamente el 75% de los tumores primarios son neopla- sias benignas, de las cuales el mixoma repre- senta la mitad de los casos reportados. Esta neoplasia se observa habitualmente en adul- tos de 30 a 50 años de edad. Normalmente se presentan en aurículas cardíacas, siendo la izquierdo más afectado. Se han descrito casos familiares que originan el complejo mixomatoso, en el cual los mixomas son múl- tiples dando lugar al Síndrome de Carney. Se presenta el caso de paciente femenina de 30 años edad, cuyo cadáver fue llevado por personal del Ministerio Público a la morgue judicial de San Pedro Sula para que se le practicara la autopsia y determinar la causa de muerte. Fue llevada al hospital Dr. Mario Catarino Rivas por su esposo, con historia de dolor precordial. Con anteceden- tes previos de dolor torácico, tratada como osteocondritis, presentó falla cardíaca y falle- ció a los pocos minutos de llegar a la emer- gencia. El esposo solicitó autopsia para determinar causa de muerte, considerando que pudiera tratarse de un caso de Mal Praxis, se procede a realizar autopsia en la cual se determina la existencia de un mixoma cardiaco de 7x3 cm. en la aurícula derecha...(AU)

Carney complex with PRKAR1A gene mutation: A case report and literature review.

RATIONALE: Carney complex (CNC) is a multiple neoplasia syndrome with autosomal dominant inheritance. CNC is characterized by the presence of myxomas, spotty skin pigmentation, and endocrine overactivity. No direct correlation has been established between disease-causing mutations and phenotype. PATIENT CONCERNS: A 16-year-old boy was admitted because of excessive weight gain over 3 years and purple striae for 1 year. Physical examination revealed Cushingoid features and spotty skin pigmentation on his face, lip, and sclera. DIAGNOSES: The patient was diagnosed as Carney complex. INTERVENTIONS: the patient underwent right adrenalectomy and partial adrenalectomy of the left adrenal gland. OUTCOME: Results of imaging showed bilateral adrenal nodular hyperplasia, multiple microcalcifications of the bilateral testes, and compression fracture of the thoracolumbar spine. Histopathological results confirmed multiple pigmented nodules in the adrenal glands. DNA sequencing revealed a nonsense mutation in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A; c.205C > T). After the second adrenalectomy, the Cushingoid features disappeared, and cortisol levels returned to normal. LESSONS: Carney complex is a rare disease that lacks consistent genotype-phenotype correlations. Our patient, who carried a germline PRKAR1A nonsense mutation (c.205C > T), clinical features included spotty skin pigmentation, osteoporosis, and primary pigmented nodular adrenal disease. Adrenalectomy is the preferred treatment for Cushing syndrome due to primary pigmented nodular adrenal disease.

Manejo anestésico em ressecção de mixoma atrial esquerdo de mãe e filho e associação com Complexo Carney

Fundamentos: tumores cardiacos primários são raros, sendo a maioria deles em átrio esquerdo, benignos e podem apresentar herança autossômica dominante. A sintomatologia depende de tamanho, mobilidade e localização. A tríade clássica dos mixomas cardíacos se compõe por manifestações constitucionais, embólicas e obstrutivas. O tratamento da escolha é a intervenção cirúrgica. O mixoma cardiaco pode estar presente no complexo de Carney, uma síndrome autossômica dominante rara, cursando com tumores endócrinos múltiplos e lesões mucocutâneas pigmentadas.Relato de Caso: CSAS, 14 anos, evoluiu com dor precordial, dispnéia aos pequenos esforços e hipertensão de difícil controle. O ecocardiograma transtorácico evidenciou mixoma de átrio esquerdo. Realizada ressecção cirúrgica. Foi diagnosticado com síndrome de Carney, sendo submetido à adrenalectomia bilateral em segundo tempo. Sua mãe SSA, 40 anos, assintomática, realizou rastreamento, evidenciando, também mixoma de átrio esquerdo, também submetida à remoção cirùrgica. Ambos foram submetidos à remoção de mixoma atrial esquerdo, com indução anestésica com fentanil, etomidato, cisatracúrio e lidocaína; intubação orotraqueal seguida de manutenção com sevoflurano. Controle rigoroso de níveis pressóricos e complicações embólicas; procedimento cirúrgico e circulação extracorpórea sem intercorrências. Em segundo tempo, realizada adrenalectomia do filho, com sucesso. Conclusão: O sucesso do manejo do mixoma atrial requer considerações multimodais, envolvendo todo o processo de diagnóstico e acompanhamento clínico dos pacientes, planejamento anestésico, ato cirúrgico curatico e investigação das complicações e de possíveis síndromes associadas.Palavras-chave: mixoma atrial, Complexo de Carney, Anestesia para cirurgia cardíaca, tumores caríacos.

Síndrome incompleto de Carney / Incomplete Carney's triad

El síndrome de Carney es una enfermedad rara, con diferentes formas de presentación, que afecta principalmente al sexo femenino y es asintomática en la mayoría de los casos. Se caracteriza por la aparición de tumores, generalmente benignos, principalmente en el pulmón, la glándula suprarrenal y el estómago; sin embargo, se pueden afectar otros órganos como el esófago. Su tratamiento es principalmente quirúrgico. Se presenta el caso de una paciente con síndrome incompleto de Carney, manejada quirúrgicamente, con excelente resultado posoperatorio. Se hace una revisión de la literatura científica actual.

Carney's triad is a rare condition with multimodal presentations, which affects mainly females and remains asymptomatic in most cases. It is characterized by the appearance of tumors, usually benign, in lung, adrenal, and stomach, but it can also affect other organs like the esophagus. Treatment of these lesions is primarily surgical. The objective of this paper is to review the current literature and to report a case of an incomplete Carney's triad managed surgically with excellent postoperative results.

Síndromes lentiginosos familiares / Family lentiginous syndromes

Los síndromes lentiginosos familiares (SLF)involucran un amplio espectro fenotípico, que abarcadesde una predisposiciónhereditaria a desarrollar lentigos sinenfermedad sistémica hasta un riesgo incrementado en la formación de hamartomas, hiperplasias y otras neoplasias.El prototipo de SLF es el síndrome de Peutz-Jeghers, pero también se incluyen dentro de este grupo de patologías el complejo de Carney, el síndrome LEOPARD, el síndrome de Bannayan-Riley-Ruvalcaba, la enfermedad de Cowden, el síndrome de Laugier-Hunziker, la disección arterial con lentiginosis y las lentiginosis benignas (lentiginosis unilateral parcial y centrofacial).La presencia de lentigos es uno de los hallazgos semiológicos más prominentes en estos cuadros y probablemente, más que una característica clínica asociada, sea el reflejo de la convergencia entre vías de señalización de importancia crucial para la embriogénesis, la diferenciación de la cresta neural, el crecimiento de los órganos diana y el funcionamiento de una amplia gama de tejidos.En el presente trabajo se realiza una descripción detallada de cada uno de los SLF, incluyendo el mecanismo molecular involucrado, las manifestaciones clínicas, la metodología diagnóstica, el seguimiento y el tratamiento.

Familial lentiginosis syndromes involve a broad phenotypic spectrum that includesfrom hereditary predisposition to presentlentigines without systemic disease to the increased risk of hamartomas, hyperplasia and other malignancies development.The prototype is Peutz-Jeghers syndrome, but Carney complex, LEOPARD syndrome, Bannayan-Riley-Ruvalcaba syndrome, Cowden's disease, Laugier-Hunziker syndrome, arterial dissection with lentigines and benign lentiginosis (partial and unilateral centrofaciallentigines) are also included in this group.The presence of lentigines is the most relevant finding and probably more than a clinical feature associated represents a reflection of the convergence of crucial signaling pathways that are important to embryogenesis, differentiation of the neural crest, target organs growth and funcional of a wide range of tissues.In this paper we perform a detailed description of these syndromes, including the molecular mechanisms involved, clinical manifestationsdiagnostic procedures, monitoring, and treatment.

Complexo de Carney esporádico com tumor testicular e mixoma atrial: relato de caso / Sporadic Carney complex with testicular tumor and atrial myxoma: case report

O complexo de Carney é uma rara forma de neoplasia endócrina múltipla familial autossômica dominante. Está associado à alteração de pigmentação cutânea e mucosa, doença nodular adrenal pigmentosa primária, mixomas cardíacos e cutâneos, adenomas hipofisários funcionantes, neoplasia testicular, adenoma ou carcinoma de tireoide, além de cistos ovarianos. Aproximadamente 70% dos indivíduos diagnosticados com complexo de Carney têm pais afetados, e 30% apresentam forma esporádica. O objetivo deste estudo foi relatar um caso de complexo de Carney esporádico por mixoma cardíaco e tumor testicular. Ressalta-se a importância do caso por sua raridade e sua forma curiosa de apresentação. Homem, 33 anos, manifestou dois quadros de acidentes vasculares cerebrais em 4 meses. Na investigação apresentou pressão arterial elevada com sopro sistólico discreto e fraqueza muscular (força grau 4 em membro superior direito e grau 3 em membro inferior direito). História mórbida de tumor testicular de células de Sertoli há 7 anos com orquiectomia bilateral. História familiar sem particularidades. Na investigação, evidenciaram-se sobrecarga atrial esquerda ao eletrocardiograma e massa tumoral pedunculada compatível com mixoma atrial esquerdo ao ecocardiograma transesofágico. Foi configurada síndrome de Carney pela presença de dois critérios maiores, e o paciente foi submetido à atriotomia esquerda, com ressecção da massa tumoral e confirmação anatomopatológica. A curiosa apresentação do caso recorda que, diante de um caso de acidente vascular cerebral em paciente jovem, a suspeita clínica seja direcionada a causas mais raras. O complexo de Carney esporádico é raro, dificultando ainda mais a elucidação.

Carney complex is a rare form of autosomal dominant multiple endocrine neoplasia familial. Changing skin pigmentation and mucos, primary pigmented nodular adrenal disease, cardiac and cutaneous myxomas, functioning pituitary adenomas, testicular cancer, thyroid adenoma or carcinoma is associated, and ovarian cysts. Approximately 70% of individuals diagnosed with Carney complex have affected parents and 30% have sporadically. The aim of this study was to report a case of sporadic Carney complex due to cardiac myxoma and testicular tumor. We emphasized the importance of the case for its rarity and curious form of presentation. Man, 33, showed two episodes of strokes in 4 months. In research presented high blood pressure with mild systolic murmur and muscle weakness (grade 4 strengthin the right arm and grade 3 in the right lower limb). Morbid history of testicular Sertoli cell tumor 7 years ago with bilateral orchiectomy. No special family history. On investigation, left atrial enlargement and was evident on the electrocardiogram, and transesophageal echocardiogram revealed the presence of pedunculated tumor mass setting a left atrial myxoma. Carney's syndrome was characterized by the existence of two major criteria and patient underwent left atriotomy with resection of the tumor mass and anatomic-pathologic confirmation. The curious case presentation reminded us that before a case of stroke in a young patient should direct the clinical suspicion for rarer causes. The Carney complex sporadic is rare, yet difficult to elucidate.