Carney triad is a synchronous or metachronous association of gastric gastrointestinal stromal tumors (GIST), pulmonary chondroma and extra-adrenal paraganglioma. The majority of patients have only one or two components of the triad, all three tumors being found in only about 2% of the patients at the time of the first diagnosis. The most common combination is gastric and pulmonary tumors. Read More
Understanding the infrared (IR) spectral response of materials as a function of their morphology is not only of fundamental importance but also of contemporary practical need in the analysis of biological and synthetic materials. While significant work has recently been reported in understanding the spectra of particles with well-defined geometries, we report here on samples that consist of collections of particles. First, we theoretically model the importance of multiple scattering effects and computationally predict the impact of local particles' environment on the recorded IR spectra. Read More
Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome, especially the isolated form without Carney complex, associated with germline mutations in PRKAR1A, the protein kinase A regulatory subunit type 1 alpha gene. We report a 31-year-old female who presented with secondary amenorrhea, cushingoid appearance, and hypertension without Carney complex. Biochemical laboratory examinations confirmed the ACTH-independent adrenal Cushing syndrome with negative Liddle test. Read More
Carney Complex (CNC) is a multiple neoplasia syndrome characterized by skin tumors and pigmented lesions, myxomas, and various endocrine tumors. The aim of this case report was to describe a case of CNC with a novel PRKAR1A mutation. A man aged 46 years with a medical history of surgery for cardiac myxomas at the age of 39 was admitted to our hospital because of four newly-developed heart masses. Read More
Purpose: Growth hormone (GH)-producing pituitary adenomas (PAs) in childhood or young adulthood are rare, and the details surrounding these tumors remain enigmatic. We present the clinical, pathological and genetic features of this disease.
Methods: We identified 25 patients aged 20 years or younger with GH-producing PAs who underwent surgery between 2003 and 2016 at Toranomon Hospital in Tokyo. Read More
Pigmented epithelioid melanocytoma (PEM) is a tumor encompassing epithelioid blue nevus of Carney complex (EBN of CNC) and was previously termed animal-type melanoma. Histologically PEMs are heavily pigmented spindled and epithelioid dermal melanocytic tumors with infiltrative borders, however, their origin remains unclear. Stem cells for the epidermis and hair follicle are located in the bulge area of the hair follicle with the potential to differentiate into multiple lineages. Read More
Departments of *Pathology §Dermatopathology ∥Dermatology †Clinical Cancer Genomics Laboratory ‡Helen Diller Cancer Center, University of California, San Francisco, CA ¶Department of Pathology, Lahey Clinic, Burlington, MA.
Pigmented epithelioid melanocytoma (PEM) is a rare cutaneous melanocytic tumor first described as epithelioid blue nevus in patients with the Carney Complex (CC). PEM was among the first established examples of an intermediate class of melanocytic tumors, including atypical Spitz tumors, with frequent metastasis to lymph nodes but only rare extranodal spread. Sporadic and CC-associated PEM are essentially histologically indistinguishable. Read More
In this report, we review the relationship between succinate dehydrogenase (SDH) deficiency and the epigenome, especially with regards to two clinical conditions. Carney triad (CT) is a very rare disease with synchronous or metachronous occurrence of at least three different tumor entities; gastric gastrointestinal stromal tumor (GIST), paraganglioma (PGL), and pulmonary chondroma. This condition affects mostly females and it is never inherited. Read More
Carney complex is a rare genetic disease characterised by a complex of myxomas, spotty pigmentation and endocrine overactivity. At diagnosis, about one-third of male patients presents with testicular tumours, namely large cell calcifying Sertoli cell tumours, which are often multicentric and/or bilateral and have a low malignant potential. Although radical orchiectomy is the gold standard for the treatment of testicular neoplasms, a conservative approach with partial orchiectomy or tumourectomy may be the best treatment option for these patients, allowing the preservation of endocrine function, fertility and body image. Read More
Objective: As the number of commercially available wound dressings is increasing rapidly, it is important for clinicians to understand the strengths and limitations of each and to recognise relationships between wound type and dressing properties to obtain optimal healing results. Our aim is to test the antimicrobial activity of two dressings.
Method: A hydroconductive (HC) dressing and a silver-impregnated foam (SIF) dressing were compared for their potential to reduce the levels meticillin-resistant Staphylococcus aureus (MRSA). Read More
Background: Mesh infection after abdominal hernia repair is a devastating complication that affects general and plastic surgeons alike. The purpose of this study was 3-fold: (1) to determine current evidence for treatment of infected abdominal wall mesh via systematic review of literature, (2) to analyze our single-institution experience with treatment of infected mesh patients, and (3) to establish a framework for how to approach this complex clinical problem.
Methods: Literature search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, followed by single-institution retrospective analysis of infected mesh patients. Read More
The identification of at-risk kindreds facilitates screening and risk reduction strategies for patients with hereditary cancer predisposition syndromes. Recently, immunohistochemistry (IHC) has emerged as a cost-effective strategy for detecting or inferring the presence of mutations in both tumors and the germline of patients presenting with tumors associated with hereditary cancer predisposition syndromes. In this review we discuss the use of novel IHC markers, including PRKAR1A, β-catenin, SDHB, fumarate hydratase and 2SC, HRASQ61R, BAP1, parafibromin and glucagon, which have either established applications or show promise for surgical pathologists to complement morphological or clinical suspicion of hereditary cancer predisposition syndromes. Read More
PurposeCurrent clinical genomics assays primarily utilize short-read sequencing (SRS), but SRS has limited ability to evaluate repetitive regions and structural variants. Long-read sequencing (LRS) has complementary strengths, and we aimed to determine whether LRS could offer a means to identify overlooked genetic variation in patients undiagnosed by SRS.MethodsWe performed low-coverage genome LRS to identify structural variants in a patient who presented with multiple neoplasia and cardiac myxomata, in whom the results of targeted clinical testing and genome SRS were negative. Read More
J Surg Res 2017 Jun 8;214:93-101. Epub 2017 Mar 8.
Department of Pediatric Surgery, Vanderbilt Children's Medical Center, Nashville, Tennessee; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pediatrics, Vanderbilt Children's Medical Center, Nashville, Tennessee.
Background: Patient portals are online applications that allow patients to interact with healthcare organizations and view information. Portal messages exchanged between patients and providers contain diverse types of communications, including delivery of medical care. The types of communications and complexity of medical decision-making in portal messages sent to surgeons have not been studied. Read More
The failure of the polycystins (PCs) to function in primary cilia is thought to be responsible for autosomal dominant polycystic kidney disease (ADPKD). Primary cilia integrate multiple cellular signaling pathways, including calcium, cAMP, Wnt, and Hedgehog, which control cell proliferation and differentiation. It has been proposed that mutated PCs result in reduced intracellular calcium, which in turn upregulates cAMP, protein kinase A (PKA) signaling, and subsequently other proliferative signaling pathways. Read More
Large-cell calcifying Sertoli cell tumor (LCCSCT) of the testis is an exceptionally rare lesion, found sparsely in any medical literature. There is a correlation between this entity and Peutz-Jeghers syndrome and Carney complex (40% of tumors). The remaining 60% of tumors are sporadic. Read More
Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Read More
Context: Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. Read More
Aims: Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive hypocellular myxoid stroma, and occur sporadically or in the context of Carney complex, an inheritable condition caused by PRKAR1A-inactivating germline mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12 mutations in the stromal components of the lesions. The aim of this study was to investigate the genomic landscape of MFAs and compare it with that of conventional FAs. Read More
The management of AF represents a major challenge in patients with CLL, especially in elderly patients with multiple comorbidities who are representative of the majority of patients with CLL. This is especially complex in the case of ibrutinib. Many anticoagulants have potential for pharmacological interaction with ibrutinib, and ibrutinib itself has antiplatelet properties. Read More
A 14-year-old male was referred for dyslipidemia. His findings were consistent with metabolic syndrome. Although he lacked the typical physical appearance, his accelerated weight gain combined with a decreased linear growth velocity suggested Cushing syndrome. Read More
Endocrinol Metab Clin North Am 2017 Jun 18;46(2):335-374. Epub 2017 Mar 18.
Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Electronic address:
Although most of pituitary adenomas are benign, they may cause significant burden to patients. Sporadic adenomas represent the vast majority of the cases, where recognized somatic mutations (eg, GNAS or USP8), as well as altered gene-expression profile often affecting cell cycle proteins have been identified. More rarely, germline mutations predisposing to pituitary adenomas -as part of a syndrome (eg, MEN1 or Carney complex), or isolated to the pituitary (AIP or GPR101) can be identified. Read More
Background: Pigmented epithelioid melanocytoma (PEM) is an uncommon, recently described entity with unknown biologic behavior. There is a high rate of regional metastases, but limited evidence of distant metastases or disease-related death.
Objective: We sought to report our series of patients given a diagnosis of PEM at our institution and provide mutational analysis of genes commonly implicated in melanoma in 2 cases. Read More
Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High-throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Read More
The syndrome of Familial Non Medullary Thyroid Carcinoma (FNMTC) includes two or more patients with an isolated non-medullary thyroid cancer (papillary, follicular, anaplastic) within the same family. To diagnose FNMTC, the clinician must exclude a syndromic presentation such as the syndromes of Cowden, Gardner or Werner, and the Carney Complex. Up to now, a hundred families with FNMTC have been genetically studied, including forms with (Ch19p13. Read More
Cardiac myxoma is the most common cardiac tumour. Most lesions occur sporadically, but occasional lesions develop in patients with Carney complex, a syndrome characterized by cardiac myxoma, spotty pigmentation, and endocrine overactivity. Two-thirds of patients with Carney complex harbour germline mutations in PRKAR1A, which encodes the type I regulatory subunit of protein kinase A (PKA). Read More
Carney complex accounts for up to two-thirds of familial cardiac myxoma. It is a rare autosomal dominant syndrome, which is also characterized by multiple mucocutaneous lesions and endocrine tumors. We report on three first-degree relatives who underwent surgical resection at the same Australian tertiary institution. Read More
Carney complex syndrome is an autosomal dominant familial tumor syndrome first described by Carney et al. in 1985. The diagnostic criteria include endocrine hyperactivity and spotty skin pigmentation. Read More
Carney Complex (CNC) is a rare autosomal dominant condition with characteristic clinical presentation, tumor development, and unique genetic mutation. We present a unique case and literature review of CNC in which two neoplasms characteristic of this complex were initially diagnosed through cytological fine needle aspirate specimens, leading to the identification of CNC, with subsequent surgical and cytogenetic confirmation. Diagn. Read More
We report a case of a 20-year-old patient with Cushing's syndrome as a component of Carney syndrome. Carney syndrome is an autosomal dominant disease with co-existing bilateral pigmented nodular adrenal disease, heart and skin myxoma, skin pigmentation, breast fibroadenoma, testicular and ovarian tumours, thyroid tumours, and pituitary adenomas. (Endokrynol Pol 2017; 68 (1): 70-72). Read More
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract although they are much less frequent than epithelial tumors. In more than 60% of cases they occur in the stomach. Especially small lesions measuring ≤1 cm in diameter, so-called microscopic GIST can occur multifocally, frequently in the proximal stomach wall and sometimes as an incidental finding in a gastrectomy specimen resected for gastric cancer. Read More
Objective: Insomnia-specific rumination has presented in subjects with insomnia. Research has identified hyperarousal as a key factor, with both trait and state components. It has been shown that emotion dysregulation also plays a role in insomnia. Read More
Informaticians are challenged to design health information technology (IT) solutions for complex problems, such as health disparities, but are achieving mixed results in demonstrating a direct impact on health outcomes. This presentation of collective intelligence and the corresponding terms of smart health, knowledge ecosystem, enhanced health disparities informatics capacities, knowledge exchange, big-data, and situational awareness are a means of demonstrating the complex challenges informatics professionals face in trying to model, measure, and manage an intelligent and smart systems response to health disparities. A critical piece in our understanding of collective intelligence for public and population health rests in our understanding of public and population health as a living and evolving network of individuals, organizations, and resources. Read More
Public health informatics is an evolving domain in which practices constantly change to meet the demands of a highly complex public health and healthcare delivery system. Given the emergence of various concepts, such as learning health systems, smart health systems, and adaptive complex health systems, health informatics professionals would benefit from a common set of measures and capabilities to inform our modeling, measuring, and managing of health system "smartness." Here, we introduce the concepts of organizational complexity, problem/issue complexity, and situational awareness as three codependent drivers of smart public health systems characteristics. Read More
Issue Medical educators and educational researchers continue to improve their processes for managing medical student and program evaluation data using sound ethical principles. This is becoming even more important as curricular innovations are occurring across undergraduate and graduate medical education. Dissemination of findings from this work is critical, and peer-reviewed journals often require an institutional review board (IRB) determination. Read More
Fibrolamellar carcinoma is a unique type of hepatocellular carcinoma with a distinctive predilection for young patients without underlying liver disease, characteristic large neoplastic cells with intervening, dense fibrosis, co-expression of keratin 7 and CD68 and activation of protein kinase A (most often by formation of DNAJB1-PRKACA). Fibrolamellar carcinoma has a similar prognosis to conventional hepatocellular carcinomas arising in non-cirrhotic livers. The current American Joint Cancer Committee staging system does not provide optimal stratification of patients with fibrolamellar carcinoma and an alternate systems should be considered in the future. Read More
Objective: Restless legs syndrome (RLS) is a common neurological movement disorder occurring in approximately 10% of the general population. The prevalence of moderately severe RLS is 2.7% overall (3. Read More
Tantalum (Ta), hafnium (Hf), and tungsten (W) analyses from complex matrices require high purification of these analytes from each other and major/trace matrix constituents, however, current state-of-the-art Ta/Hf/W separations rely on traditional anion exchange approaches that show relatively similar distribution coefficient (Kd) values for each element. This work reports an assessment of three commercially available extraction chromatographic resins (TEVA, TRU, and UTEVA) for Ta/Hf/W separations. Batch contact studies show differences in Ta/Hf and Ta/W Kd values of up to 10(6) and 10(4) (respectively), representing an improvement of a factor of 100 and 300 in Ta/Hf and Ta/W Kd values (respectively) over AG1×4 resin. Read More
Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated with intense production of proinflammatory cytokines, but whether this cytokine storm is the main cause of fatality or is a consequence of extensive virus replication that itself drives disease remains controversial. Conventional intratracheal inoculation of a liquid suspension of H5N1 influenza virus in nonhuman primates likely results in efficient clearance of virus within the upper respiratory tract and rarely produces severe disease. Read More
Background: Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal abnormalities (CLOVES) is a complex overgrowth syndrome with dramatic aesthetic and functional implications. The truncal masses characteristic of CLOVES syndrome are described as vascular malformations or lipomatous lesions with variable vascular components. Herein, we describe our single-institution experience with surgical excision of CLOVES-related truncal masses and discuss future directions in treatment of these complex anomalies. Read More
Melanotic schwannoma (MS) is a soft tissue neoplasm that shares histologic features with melanocytic tumors and schwannomas. A type of MS, called psammomatous MS (PMS), is associated with Carney complex (CNC), which is caused by PRKAR1A mutations. Other pigmented neoplasms, such as uveal melanomas and melanocytomas (MCs), are associated with genetic defects in other genes including GNA11. Read More
Osteochondromyxoma is an extremely rare bone tumor associated with 1% of Carney complex patients and constitutes one of its 11 diagnostic criteria. This narrative review of osteochondromyxoma is based on a search of all references to the topic in PubMed, Web Of Science, SCOPUS, ScienceDirect, and JSTOR databases. Special attention was focused on case reports, leading to a review encompassing the case reports to date, as well as related animal model studies. Read More
We often think of the lentiginoses, phacomatoses and other neurocutaneous syndromes as conditions that affect the skin and also predispose to a variety of tumors. However, we rarely think of Peutz-Jeghers syndrome (PJS), Carney complex (CNC), Cowden disease (CD), neurofibromatosis type-1 (NF-1) or tuberous sclerosis (TSC) as conditions that are multiple endocrine neoplasias (MEN). Indeed, all of these conditions predispose to a variety of endocrine tumors, in addition to many other neoplasms. Read More
Carney complex is a familial lentiginosis syndrome; these disorders cover a wide phenotypic spectrum ranging from a benign inherited predisposition to develop cutaneous spots not associated with systemic disease to associations with several syndromes. Carney complex is caused by PRKAR1A mutations and perturbations of the cyclic AMP-dependent protein kinase (PKA) signaling pathway. In addition to the cutaneous findings, the main tumors associated with Carney complex are endocrine: 1) primary pigmented nodular adrenocortical disease, a bilateral adrenal hyperplasia leading to Cushing syndrome; 2) growth-hormone secreting pituitary adenoma or pituitary somatotropic hyperplasia leading to acromegaly; 3) thyroid and gonadal tumors, including a predisposition to thyroid cancer. Read More
*Department of Internal Medicine †Division of Endocrinology, Diabetes, Metabolism and Nutrition §Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN ‡Section on Endocrinology and Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
Carney complex (CNC) is a rare dominantly inherited multiorgan tumoral disorder that includes Cushing syndrome (CS). To establish the Mayo Clinic experience with the CS component, including its clinical, laboratory, and pathologic findings, we performed a retrospective search of the patient and pathologic databases of Mayo Clinic in Rochester, MN, for patients with CNC and clinical or laboratory findings of CS. Thirty-seven patients with CNC were identified. Read More