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Turkish Journal of Medical Sciences Nov 2020Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder that is characterized by cellular and tissue dysplasia in several organs. With the advent... (Review)
Review
Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder that is characterized by cellular and tissue dysplasia in several organs. With the advent of genetic and molecular techniques, mutations in the TSC1 or TSC2 genes were discovered to be responsible for mTOR overactivation, which is the underlying mechanism of pathogenesis. TSC is a highly heterogenous clinical entity with variable presentations and severity of disease. The brain, heart, skin, eyes, kidneys, and lungs are commonly involved in this syndrome, with neurologic symptoms comprising a significant source of morbidity and mortality. In 2012, the diagnostic criteria for TSC were revised by the International Tuberous Sclerosis Complex Consensus panel, and genetic testing was incorporated into the guidelines. Early detection of cardiac rhabdomyomas or TSC-associated skin lesions can suggest the diagnosis and underlie the importance of clinical vigilance. Animal studies have demonstrated the benefit of using mTOR inhibitors for various symptoms of TSC, and they have been successfully translated into clinical trials with significant improvement in symptom burden. Subependymal giant cell astrocytomas, renal angiomyolipomas, and epilepsy are the three FDA-approved indications in relation to TSC for the use of everolimus, which is a first generation mTOR inhibitor. Rapamycin has been FDA approved for lymphangioleiomyomatosis. Other TSC symptoms that could potentially benefit from this class of medication are currently under investigation. TSC constitutes a unique combination of protean physical symptoms and neurobehavioral abnormalities. TSC associated neuropsychiatric disorders (TAND), including intellectual disability, mood disorders, and autism spectrum disorder, represent significant challenges but remain underdiagnosed and undertreated. The TAND checklist is a useful tool for routine use in the clinical evaluation of TSC patients. A multidisciplinary treatment plan, based on the specific problems and needs of individuals, is the key to management of this genetic condition. Ongoing research studies have been providing promising leads for developing novel mechanistic strategies to address the pathophysiology of TSC.
Topics: Animals; Brain; Epilepsy; Humans; TOR Serine-Threonine Kinases; Tuberous Sclerosis; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein
PubMed: 32222129
DOI: 10.3906/sag-2002-133 -
Journal of Cardiovascular Echography 2022Studying cardiac masses is one of the most challenging tasks for cardiac imagers. The aim of this review article is to focus on the modern imaging of cardiac masses... (Review)
Review
Studying cardiac masses is one of the most challenging tasks for cardiac imagers. The aim of this review article is to focus on the modern imaging of cardiac masses proceeding through the most frequent ones. Cardiac benign masses such as myxoma, cardiac papillary fibroelastoma, rhabdomyoma, lipoma, and hemangioma are browsed considering the usefulness of most common cardiovascular imaging tools, such as ultrasound techniques, cardiac computed tomography, cardiac magnetic resonance, and in the diagnostic process. In the same way, the most frequent malignant cardiac masses, such as angiosarcoma and metastases, are highlighted. Then, the article browses through nontumoral masses such as cysts, mitral caseous degenerative formations, thrombi, and vegetations, highlighting the differential diagnosis between them. In addition, the article helps in recognizing anatomic normal variants that should not be misdiagnosed as pathological entities.
PubMed: 36249434
DOI: 10.4103/jcecho.jcecho_18_22 -
Head and Neck Pathology Dec 2021This report describes a case of an adult rhabdomyoma (ARM) occurring in the oral cavity. A 47-year-old man was referred for the diagnosis of a painless,...
This report describes a case of an adult rhabdomyoma (ARM) occurring in the oral cavity. A 47-year-old man was referred for the diagnosis of a painless, well-circumscribed, submucous nodule located on the floor of the mouth, measuring approximately 6.0 cm in length. Computed tomography revealed a well-defined, solid, and hypodense mass. A benign salivary gland or mesenchymal tumor were the main diagnostic hypotheses. Under local anesthesia, the patient underwent surgical excision. Microscopically, the tumor comprised large polygonal well-defined cells with abundant, eosinophilic granular cytoplasm with cross striations. No atypia or mitosis was observed. The cells were positive for muscle-specific actin, desmin, and sarcomeric alpha-actin. Based on these features, a diagnosis of ARM was established. No recurrence was observed after 48 months. Although rare, ARM should be considered in the differential diagnosis of oral submucosal nodules, especially those located on the floor of the mouth.
Topics: Humans; Male; Middle Aged; Mouth Neoplasms; Rhabdomyoma
PubMed: 34378165
DOI: 10.1007/s12105-021-01371-z -
Cureus Apr 2021Cardiac rhabdomyoma is a hamartoma comprised of cardiac myocytes. It is the classic cardiac manifestation of tuberous sclerosis complex (TSC) which is an autosomal...
Cardiac rhabdomyoma is a hamartoma comprised of cardiac myocytes. It is the classic cardiac manifestation of tuberous sclerosis complex (TSC) which is an autosomal dominant genetic syndrome with multi-organ involvement, but highly variable phenotype. Cardiac rhabdomyoma is most commonly diagnosed in infancy, 70 to 90% of whom have TSC. However, TSC-associated cardiac rhabdomyoma usually shows spontaneous regression within the first two years of life and hence is extremely rare in adults. We present a 34-year-old woman with TSC who was found to have a cardiac rhabdomyoma when she was referred to the cardiology clinic for evaluation and to establish care. Cardiac rhabdomyoma is usually asymptomatic. However, depending on size and location, it can cause outflow or inflow tract obstruction and aberrant electrical conduction. Hence, appropriate surveillance is important.
PubMed: 34026381
DOI: 10.7759/cureus.14565 -
Head and Neck Pathology Mar 2023Oncocytes are a component of many metaplastic and neoplastic lesions throughout the head and neck area, primarily originating in salivary/seromucinous glands and the... (Review)
Review
BACKGROUND
Oncocytes are a component of many metaplastic and neoplastic lesions throughout the head and neck area, primarily originating in salivary/seromucinous glands and the thyroid gland. In addition, other lesions can contain cells that mimic oncocytes (pseudo-oncocytes); these can be of epithelial or non-epithelial origin.
METHODS
Review article.
RESULTS
Oncocytic metaplasia is common in seromucinous glands throughout the upper aerodigestive tract, most notable in the oral cavity, nasopharynx and larynx. The main oncocytic salivary gland neoplasms are Warthin tumor and oncocytoma. Infarction of Warthin tumor may lead to recognition difficulties. Oncocytic subtypes of mucoepidermoid carcinoma and intraductal carcinoma have morphologic and immunohistochemical features that allow distinction from major oncocytic entities. Oncocytic thyroid tumors include adenoma, carcinoma (follicular, papillary and medullary), along with poorly differentiated tumors. Oncocytic papillary sinonasal and middle ear tumors must be distinguished from low grade adenocarcinomas. Pseudo-oncocytic entities include paraganglioma, Langerhans cell histiocytosis, giant cell tumor, rhabdomyoma, and metastatic tumors.
CONCLUSIONS
Correct diagnosis of oncocytic head and neck lesions requires a knowledge of the spectrum of possible entities, their characteristic sites of occurrence, architecture, histomorphology, and immunohistochemistry. Oncocytic subtypes of several newly described entities are now recognized. Both epithelial and non-epithelial mimics of oncocytes exist. The molecular features of oncocytic tumors can be helpful in their diagnosis and understanding their pathogenesis.
Topics: Humans; Oxyphil Cells; Adenolymphoma; Salivary Gland Neoplasms; Salivary Glands; Adenoma, Oxyphilic
PubMed: 36928735
DOI: 10.1007/s12105-022-01520-y -
Pharmacological Research Sep 2023Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterised by abnormal cell proliferation and differentiation that affects multiple organs and can... (Review)
Review
Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterised by abnormal cell proliferation and differentiation that affects multiple organs and can lead to the growth of hamartomas. Tuberous sclerosis complex is caused by the disinhibition of the protein mTOR (mammalian target of rapamycin). In the past, various therapeutic approaches, even if only symptomatic, have been attempted to improve the clinical effects of this disease. While all of these therapeutic strategies are useful and are still used and indicated, they are symptomatic therapies based on the individual symptoms of the disease and therefore not fully effective in modifying long-term outcomes. A new therapeutic approach is the introduction of allosteric inhibitors of mTORC1, which allow restoration of metabolic homeostasis in mutant cells, potentially eliminating most of the clinical manifestations associated with Tuberous sclerosis complex. Everolimus, a mammalian target of the rapamycin inhibitor, is able to reduce hamartomas, correcting the specific molecular defect that causes Tuberous sclerosis complex. In this review, we report the findings from the literature on the use of everolimus as an effective and safe drug in the treatment of TSC manifestations affecting various organs, from the central nervous system to the heart.
Topics: Humans; Everolimus; Tuberous Sclerosis; Sirolimus; Mechanistic Target of Rapamycin Complex 1
PubMed: 37549757
DOI: 10.1016/j.phrs.2023.106884