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Indian Journal of Dermatology 2018Multiple cutaneous and uterine leiomyomatosis (MCUL), also known as Reed's syndrome, is a rare genodermatosis, with an autosomal dominant pattern of inheritance. It...
Multiple cutaneous and uterine leiomyomatosis (MCUL), also known as Reed's syndrome, is a rare genodermatosis, with an autosomal dominant pattern of inheritance. It results from a germline heterozygous mutation of fumarate hydratase gene, that is classified as a tumor suppressor gene. Hereditary leiomyomatosis and renal cell cancer is characterized by the association of MCUL with renal cell carcinoma. We report a case of a 57-year-old woman, with multiple cutaneous leiomyomas as the presenting sign of Reed's syndrome.
PubMed: 29937565
DOI: 10.4103/ijd.IJD_69_18 -
Cancers May 2019Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors that show the highest heritability of all human neoplasms and represent a paradoxical example... (Review)
Review
Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors that show the highest heritability of all human neoplasms and represent a paradoxical example of genetic heterogeneity. Amongst the elevated number of genes involved in the hereditary predisposition to the disease (at least nineteen) there are eleven tricarboxylic acid (TCA) cycle-related genes, some of which are also involved in the development of congenital recessive neurological disorders and other cancers such as cutaneous and uterine leiomyomas, gastrointestinal tumors and renal cancer. Somatic or germline mutation of genes encoding enzymes catalyzing pivotal steps of the TCA cycle not only disrupts cellular respiration, but also causes severe alterations in mitochondrial metabolite pools. These latter alterations lead to aberrant accumulation of "oncometabolites" that, in the end, may lead to deregulation of the metabolic adaptation of cells to hypoxia, inhibition of the DNA repair processes and overall pathological changes in gene expression. In this review, we will address the TCA cycle mutations leading to the development of PPGL, and we will discuss the relevance of these mutations for the transformation of neural crest-derived cells and potential therapeutic approaches based on the emerging knowledge of underlying molecular alterations.
PubMed: 31100940
DOI: 10.3390/cancers11050683 -
Clinical Medicine (London, England) Dec 2017This article provides an overview of selected genetic skin conditions where multiple inherited cutaneous tumours are a central feature. Skin tumours that arise from skin... (Review)
Review
This article provides an overview of selected genetic skin conditions where multiple inherited cutaneous tumours are a central feature. Skin tumours that arise from skin structures such as hair, sweat glands and sebaceous glands are called skin appendage tumours. These tumours are uncommon, but can have important implications for patient care. Certain appendageal tumours, particularly when multiple lesions are seen, may indicate an underlying genetic condition. These tumours may not display clinical features that allow a secure diagnosis to be made, necessitating biopsy and dermatopathological assessment. Coupled with robust clinical assessment, biopsy findings can guide genetic testing as, increasingly, the causative genes are known for these conditions. Here we review illustrative examples of appendageal tumours and relevant advances made in genetic discovery, and suggest when referral to a geneticist may need to be considered.
Topics: Birt-Hogg-Dube Syndrome; DNA Mismatch Repair; Fibroma; Fumarate Hydratase; Hamartoma Syndrome, Multiple; Humans; Leiomyomatosis; Muir-Torre Syndrome; Neoplastic Syndromes, Hereditary; PTEN Phosphohydrolase; Proto-Oncogene Proteins; Skin Neoplasms; Tumor Suppressor Proteins; Uterine Neoplasms
PubMed: 29196359
DOI: 10.7861/clinmedicine.17-6-562 -
Frontiers in Endocrinology 2023Multiple Endocrine Neoplasia type 1 is a rare genetic syndrome mainly caused by mutations of gene and characterized by a combination of several endocrine and...
BACKGROUND
Multiple Endocrine Neoplasia type 1 is a rare genetic syndrome mainly caused by mutations of gene and characterized by a combination of several endocrine and non-endocrine manifestations. The objective of this study was to describe cutaneous lesions and other non-endocrine manifestations of in a cohort of patients with familial (F) and sporadic (S) , compare the prevalence of these manifestations between the two cohorts, and investigate the correlation with mutation status.
METHODS
We collected phenotypic and genotypic data of 185 patients with F- and S- followed from 1997 to 2022. The associations between F- and S- or mutation-positive and mutation-negative patients and non-endocrine manifestations were determined using chi-square or Fisher's exact tests or multivariate exact logistic regression analyses.
RESULTS
The prevalence of angiofibromas was significantly higher in F- than in S- in both the whole (p < 0.001) and index case (p = 0.003) cohorts. The prevalence of lipomas was also significantly higher in F- than in S- (p = 0.009) and in mutation-positive than in mutation-negative (p = 0.01) index cases. In the whole cohort, the prevalence of lipomas was significantly higher in mutation-positive compared to mutation-negative patients (OR = 2.7, p = 0.02) and in F- than in S- (p = 0.03), only after adjustment for age. No significant differences were observed for the other non-endocrine manifestations between the two cohorts. Hibernoma and collagenoma were each present in one patient (0.5%) and meningioma and neuroblastoma in 2.7% and 0.5%, respectively. Gastric leiomyoma was present in 1.1% of the patients and uterine leiomyoma in 14% of women. Thyroid cancer, breast cancer, lung cancer, basal cell carcinoma, melanoma, and colorectal cancer were present in 4.9%, 2.7%, 1.6%, 1.6%, 2.2%, and 0.5% of the whole series, respectively.
CONCLUSIONS
We found a significantly higher prevalence of angiofibromas and lipomas in F- compared with S- and in mutation-positive compared to mutation-negative patients. In patients with one major endocrine manifestation of , the presence of cutaneous lesions might suggest the diagnosis of and a possible indication for genetic screening.
Topics: Humans; Female; Multiple Endocrine Neoplasia Type 1; Angiofibroma; Genetic Testing; Mutation; Lipoma
PubMed: 37484956
DOI: 10.3389/fendo.2023.1191040 -
Frontiers in Endocrinology 2023Cushing's syndrome (CS) resulting from endogenous hypercortisolism can be sporadic or can occur in the context of familial disease because of pituitary or... (Review)
Review
Cushing's syndrome (CS) resulting from endogenous hypercortisolism can be sporadic or can occur in the context of familial disease because of pituitary or extra-pituitary neuroendocrine tumors. Multiple endocrine neoplasia type 1 (MEN1) is unique among familial endocrine tumor syndromes because hypercortisolism in this context can result from pituitary, adrenal, or thymic neuroendocrine tumors and can therefore reflect either ACTH-dependent or ACTH-independent pathophysiologies. The prominent expressions of MEN1 include primary hyperparathyroidism, tumors of the anterior pituitary, gastroenteropancreatic neuroendocrine tumors, and bronchial carcinoid tumors along with several common non-endocrine manifestations such as cutaneous angiofibromas and leiomyomas. Pituitary tumors are present in about 40% of MEN1 patients, and up to 10% of such tumors secrete ACTH that can result in Cushing's disease. Adrenocortical neoplasms occur frequently in MEN1. Although such adrenal tumors are mostly clinically silent, this category can include benign or malignant tumors causing hypercortisolism and CS. Ectopic tumoral ACTH secretion has also been observed in MEN1, almost exclusively originating from thymic neuroendocrine tumors. The range of clinical presentations, etiologies, and diagnostic challenges of CS in MEN1 are reviewed herein with an emphasis on the medical literature since 1997, when the MEN1 gene was identified.
Topics: Humans; Cushing Syndrome; Multiple Endocrine Neoplasia Type 1; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; ACTH Syndrome, Ectopic; Neuroendocrine Tumors; Thymus Neoplasms; Adrenocorticotropic Hormone
PubMed: 37409236
DOI: 10.3389/fendo.2023.1183297 -
Archives of Craniofacial Surgery Mar 2017Cutaneous leiomyomas can be classified into three types according to the site of origin: piloleiomyoma, angioleiomyoma, and dartoic (genital) leiomyoma. It might be...
Cutaneous leiomyomas can be classified into three types according to the site of origin: piloleiomyoma, angioleiomyoma, and dartoic (genital) leiomyoma. It might be expected that leiomyomas are commonly found on the scalp because there are many arrector pili muscles and vessels. However, leiomyomas are actually rarely reported in the scalp. Recently, we observed a case of cutaneous leiomyoma in the scalp and present our experience along with a literature review.
PubMed: 28913307
DOI: 10.7181/acfs.2017.18.1.62 -
Acta Medica Iranica 2013Smooth muscle tumors rather benign or malignant can arise wherever the muscular tissue presents but cutaneous leiomyoma is one of the rare benign tumors of the which...
Smooth muscle tumors rather benign or malignant can arise wherever the muscular tissue presents but cutaneous leiomyoma is one of the rare benign tumors of the which even the diagnostic criteria from the malignant type of the tumor is still in doubt. This study was aimed to compare the subtypes of cutaneous leiomyoma from different histologic aspects in order to find unique criteria for better classification and diagnosis. The six year data base of our center was reviewed and 25 patients with cutaneous leiomyoma were included in this study. Of 25 patients, 5 were female and 20 were male. 5 patients had angioleiomyoma (ALM) and 20 had pilar leiomyoma (PLM). ALM had following characteristics: dilated vascular canals intermingled with compact smooth muscle bundles; well circumscribe counter and myxoid and hyaline changes through the tumor. In contrast, PLMs had following histologic features: poor defined outline, entrapped hair follicles and eccrine glands, acanthosis and elongated rete ridges with hyperpigmentation and smooth muscle bundles which are interdigitated with elongated rete ridges. Here we introduced some distinct histological features for each subtype of the cutaneous leiomyoma which can lead to create novel criteria for classification and diagnosis of the lesion.
Topics: Adult; Aged; Angiomyoma; Biopsy; Eccrine Glands; Female; Hair Follicle; Humans; Hyalin; Hyperpigmentation; Leiomyoma; Leiomyomatosis; Male; Middle Aged; Myocytes, Smooth Muscle; Predictive Value of Tests; Skin Neoplasms
PubMed: 23456580
DOI: No ID Found