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Digestion 2023Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus,... (Review)
Review
BACKGROUND
Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years.
SUMMARY
Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system.
KEY MESSAGES
Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.
Topics: Adolescent; Humans; Adult; Child; Peutz-Jeghers Syndrome; Quality of Life; Intestinal Polyps; Intestine, Small; Capsule Endoscopy
PubMed: 37054692
DOI: 10.1159/000529799 -
Annales de Dermatologie Et de... Dec 2012Lasers are a very effective approach for treating many hyperpigmented lesions. They are the gold standard treatment for actinic lentigos and dermal hypermelanocytosis,...
Lasers are a very effective approach for treating many hyperpigmented lesions. They are the gold standard treatment for actinic lentigos and dermal hypermelanocytosis, such as Ota nevus. Becker nevus, hyperpigmented mosaicisms, and lentigines can also be successfully treated with lasers, but they could be less effective and relapses can be observed. However, lasers cannot be proposed for all types of hyperpigmentation. Thus, freckles and café-au-lait macules should not be treated as the relapses are nearly constant. Due to its complex pathophysiology, melasma has a special place in hyperpigmented dermatoses. Q-switched lasers (using standard parameters or low fluency) should not be used because of consistent relapses and the high risk of post-inflammatory hyperpigmentation. Paradoxically, targeting the vascular component of the melasma lesion with lasers could have a beneficial effect. However, these results have yet to be confirmed. In all cases, a precise diagnosis of the type of hyperpigmentation is mandatory before any laser treatment, and the limits and the potential side effects of the treatment must be clearly explained to patients.
Topics: Cafe-au-Lait Spots; Facial Dermatoses; Facial Neoplasms; Humans; Hyperpigmentation; Inflammation; Laser Therapy; Lasers; Lasers, Solid-State; Lentigo; Melanins; Melanocytes; Melanosis; Nevus, Pigmented; Skin Diseases; Skin Neoplasms
PubMed: 23522632
DOI: 10.1016/S0151-9638(12)70129-1 -
World Journal of Gastroenterology Feb 2023Hereditary polyposis syndrome can be divided into three categories: Ade-nomatous, serrated, and hamartomatous polyps. Hamartomatous polyps, malformations of normal... (Review)
Review
Hereditary polyposis syndrome can be divided into three categories: Ade-nomatous, serrated, and hamartomatous polyps. Hamartomatous polyps, malformations of normal tissue presenting in a disorganized manner, are characterized by an autosomal dominant inheritance pattern. These syndromes exhibit hamartomatous gastrointestinal polyps in conjunction to extra-intestinal manifestations, which require conscientious and diligent monitoring. Peutz-Jeghers syndrome, Cowden syndrome, and juvenile polyposis syndrome are the most common displays of hamartomatous polyposis syndrome (HPS). Diagnosis can be pursued with molecular testing and endoscopic sampling. Early identification of these autosomal dominant pathologies allows to optimize malignancy sur-veillance, which helps reduce morbidity and mortality in both the affected patient population as well as at-risk family members. Endoscopic surveillance is an important pillar of prognosis and monitoring, with many patients eventually requiring surgical intervention. In this review, we discuss the diagnosis, surveillance, and management of HPS.
Topics: Humans; Neoplastic Syndromes, Hereditary; Peutz-Jeghers Syndrome; Hamartoma; Hamartoma Syndrome, Multiple; Intestinal Polyps; Polyps
PubMed: 36925460
DOI: 10.3748/wjg.v29.i8.1304 -
Archives of Pathology & Laboratory... Mar 2011Atypical lentiginous melanocytic lesions, particularly in older individuals, continue to pose a diagnostic challenge. Such lesions often show features intermediate... (Review)
Review
CONTEXT
Atypical lentiginous melanocytic lesions, particularly in older individuals, continue to pose a diagnostic challenge. Such lesions often show features intermediate between lentiginous nevus and melanoma in situ. We have recently defined within this group of lesions a histologic pattern of lentiginous melanoma, a slowly progressing variant of melanoma typically found on the trunk and proximal extremities of middle-aged and older individuals.
OBJECTIVE
To review the clinical and histologic features of lentiginous melanoma and its histologic differential diagnosis.
DATA SOURCES
Review of pertinent published literature and work in our laboratory.
CONCLUSIONS
Lentiginous melanoma defines a subset of slowly progressing melanoma occurring in middle-aged and older patients. It is histologically characterized by a broad atypical lentiginous growth pattern of moderately atypical melanocytes showing focal nesting and pagetoid spread without significant dermal fibroplasia or alteration of the rete ridges. Lentiginous melanoma shows significant overlap in clinical and histologic features with atypical lentiginous nevus (of the elderly). Relationship between these entities requires further investigations. Given the risk of progression to invasive melanoma, all lesions showing features of lentiginous melanoma should be treated with adequately wide excision.
Topics: Aged; Diagnosis, Differential; Disease Progression; Humans; Hutchinson's Melanotic Freckle; Lentigo; Melanocytes; Middle Aged; Nevus, Pigmented; Precancerous Conditions; Skin Neoplasms
PubMed: 21366457
DOI: 10.5858/2009-0538-RA.1 -
Orphanet Journal of Rare Diseases May 2008LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym... (Review)
Review
LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. About 200 patients have been reported worldwide but the real incidence of LS has not been assessed. Facial dysmorphism includes ocular hypertelorism, palpebral ptosis and low-set ears. Stature is usually below the 25th centile. Cardiac defects, in particular hypertrophic cardiomyopathy mostly involving the left ventricle, and ECG anomalies are common. The lentigines may be congenital, although more frequently manifest by the age of 4-5 years and increase throughout puberty. Additional common features are café-au-lait spots (CLS), chest anomalies, cryptorchidism, delayed puberty, hypotonia, mild developmental delay, sensorineural deafness and learning difficulties. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. LS is largely overlapping Noonan syndrome and, during childhood, Neurofibromatosis type 1-Noonan syndrome. Diagnostic clues of LS are multiple lentigines and CLS, hypertrophic cardiomyopathy and deafness. Mutation-based differential diagnosis in patients with borderline clinical manifestations is warranted. LS is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, a 50% recurrence risk is appropriate. LS should be suspected in foetuses with severe cardiac hypertrophy and prenatal DNA test may be performed. Clinical management should address growth and motor development and congenital anomalies, in particular cardiac defects that should be monitored annually. Hypertrophic cardiomyopathy needs careful risk assessment and prophylaxis against sudden death in patients at risk. Hearing should be evaluated annually until adulthood. With the only exception of ventricular hypertrophy, adults with LS do not require special medical care and long-term prognosis is favourable.
Topics: Adult; Cardiomyopathy, Hypertrophic; Child, Preschool; Face; Female; Humans; LEOPARD Syndrome; Mutation; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Skin
PubMed: 18505544
DOI: 10.1186/1750-1172-3-13 -
The New England Journal of Medicine Jan 2019
Topics: Abdominal Pain; Humans; Intestinal Polyps; Intussusception; Jejunal Diseases; Male; Middle Aged; Peutz-Jeghers Syndrome; Tomography, X-Ray Computed
PubMed: 30699321
DOI: 10.1056/NEJMicm1806623 -
The Journal of Biological Chemistry Apr 2023Liver kinase B1 (LKB1) is a serine-threonine kinase that participates in multiple cellular and biological processes, including energy metabolism, cell polarity, cell... (Review)
Review
Liver kinase B1 (LKB1) is a serine-threonine kinase that participates in multiple cellular and biological processes, including energy metabolism, cell polarity, cell proliferation, cell migration, and many others. LKB1 is initially identified as a germline-mutated causative gene in Peutz-Jeghers syndrome and is commonly regarded as a tumor suppressor due to frequent inactivation in a variety of cancers. LKB1 directly binds and activates its downstream kinases including the AMP-activated protein kinase (AMPK) and AMPK-related kinases by phosphorylation, which has been intensively investigated for the past decades. An increasing number of studies have uncovered the posttranslational modifications (PTMs) of LKB1 and consequent changes in its localization, activity, and interaction with substrates. The alteration in LKB1 function as a consequence of genetic mutations and aberrant upstream signaling regulation leads to tumor development and progression. Here, we review current knowledge about the mechanism of LKB1 in cancer and the contributions of PTMs, such as phosphorylation, ubiquitination, SUMOylation, acetylation, prenylation, and others, to the regulation of LKB1 function, offering new insights into the therapeutic strategies in cancer.
Topics: Humans; AMP-Activated Protein Kinases; Liver; Peutz-Jeghers Syndrome; Phosphorylation; Protein Serine-Threonine Kinases; Neoplasms; Protein Processing, Post-Translational
PubMed: 36870679
DOI: 10.1016/j.jbc.2023.104570 -
Best Practice & Research. Clinical... 2022Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is... (Review)
Review
Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is autosomal dominant. JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations. Among the syndromic features, JPS can present with concomitant extra-intestinal manifestations, above all cutaneous manifestations such as telangiectasia, pigmented nevi, and skeletal stigmata. Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome. In JPS a cumulative risk of CRC of 39-68% has been estimated. The oncological risk justifies and imposes prevention strategies that aim at the cancer risk reduction through endoscopic screening, as recommended by international scientific societies. The aim of this review is to summarize clinical and genetic features of JPS and to elucidate the steps of the clinical management from diagnosis to surveillance.
Topics: Colorectal Neoplasms; Gastrointestinal Neoplasms; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Peutz-Jeghers Syndrome
PubMed: 35988962
DOI: 10.1016/j.bpg.2022.101799 -
The Surgical Clinics of North America Aug 2008Since the histologic description of the hamartomatous polyp in 1957 by Horrilleno and colleagues, descriptions have appeared of several different syndromes with the... (Review)
Review
Since the histologic description of the hamartomatous polyp in 1957 by Horrilleno and colleagues, descriptions have appeared of several different syndromes with the propensity to develop these polyps in the upper and lower gastrointestinal tracts. These syndromes include juvenile polyposis, Peutz-Jeghers syndrome, hereditary mixed polyposis syndrome, and the phosphatase and tensin homolog gene (PTEN) hamartoma tumor syndromes (Cowden and Bannayan-Riley-Ruvalcaba syndromes), which are autosomal-dominantly inherited, and Cronkhite-Canada syndrome, which is acquired. This article reviews the clinical aspects, the molecular pathogenesis, the affected organ systems, the risks of cancer, and the management of these hamartomatous polyposis syndromes. Although the incidence of these syndromes is low, it is important for clinicians to recognize these disorders to prevent morbidity and mortality in these patients, and to perform presymptomatic testing in patients at risk.
Topics: Diagnosis, Differential; Digestive System Surgical Procedures; Endoscopy, Gastrointestinal; Genetic Predisposition to Disease; Humans; Peutz-Jeghers Syndrome; Prognosis
PubMed: 18672141
DOI: 10.1016/j.suc.2008.05.002 -
Current Opinion in Gastroenterology Jan 2022The goal of this review is to help providers recognize, diagnose and manage gastrointestinal (GI) polyposis syndromes. (Review)
Review
PURPOSE OF REVIEW
The goal of this review is to help providers recognize, diagnose and manage gastrointestinal (GI) polyposis syndromes.
RECENT FINDINGS
Intestinal polyps include a number of histological sub-types such as adenomas, serrated, hamartomas among others. Over a quarter of individuals undergoing screening colonoscopy are expected to have colonic adenomas. Although it is not uncommon for adults to have a few GI polyps in their lifetime, some individuals are found to have multiple polyps of varying histology throughout the GI tract. In these individuals, depending on polyp histology, number, location and size as well as extra-intestinal features and/or family history, a polyposis syndrome should be considered with appropriate testing and management.
SUMMARY
Diagnosis and management of polyposis syndromes has evolved with advent of multigene panel testing and new data on optimal surveillance strategies. Evidence-based recommendations and current practice guidelines for polyposis syndromes are reviewed here. Areas of uncertainty and future research are also highlighted.
Topics: Adenoma; Adult; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Humans; Intestinal Polyps; Peutz-Jeghers Syndrome
PubMed: 34839308
DOI: 10.1097/MOG.0000000000000796