Peutz-Jeghers Research Articles

Usefulness and limitation of ultrasound for children with Peutz–Jeghers syndrome: A case series

Usefulness and limitation of ultrasound for children with Peutz–Jeghers syndrome: A case series

Facial Features of Hereditary Cancer Predisposition.

In the age of telehealth medicine, an individual's facial features may provide the only physical clues signaling the presence of a heritable cancer predisposition syndrome. These syndromes include APC-associated polyposis, Birt-Hogg-Dubé syndrome, CYLD cutaneous syndrome, hereditary leiomyomatosis and renal cell cancer, multiple endocrine neoplasia, neurofibromatosis type 1, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome, and tuberous sclerosis complex 1 and 2, among others. Correctly identifying characteristic features is important for genetic and nongenetic specialists as early detection can enable prompt intervention, improving patient outcomes. Advancements in the availability of genetic testing allow patients and their relatives to have more information about their genetic risk profile than before. These changes in clinical pathways, combined with improvements in screening and risk-reducing treatment, highlight the need to outline the cutaneous and morphologic features of high-risk cancer syndromes for clinicians. In this review, we describe the important facial features of hereditary cancer predisposition, with emphasis on diagnosis, cutaneous and extracutaneous manifestations, and screening.

Altered mucosal bacteria and metabolomics in patients with Peutz–Jeghers syndrome

BackgroundPeutz–Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS.AimThis study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS.MethodsThe bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples.ResultsHigh-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors.ConclusionThis is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

Peutz-Jeghers Syndrome: A Case Report

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by hamartomatous gastrointestinal polyposis and mucocutaneous pigmentation. We report here the case of a 28-year-old young woman presenting with PJS revealed by an acute small bowel obstruction at the MED VI University Hospital of Marrakech. Surgical exploration revealed hamartomatous polyps necessitating segmental resection. Anatomopathological examination confirmed the diagnosis. Postoperative recovery was uneventful. Surveillance revealed no abnormalities.

Peutz-Jeghers Syndrome: A Comprehensive Review of Genetics, Clinical Features, and Management Approaches.

A relatively rare inherited condition known as Peutz-Jeghers syndrome (PJS) causes mucocutaneous pigmentation and gastrointestinal hamartomatous polyps. These polyps are non-cancerous, but the presence of PJS significantly increases the chances of developing various types of cancers, such as colorectal, pancreatic, gastric, and breast cancer. The purpose of this review article is to give an abbreviated summary of what is currently known about this syndrome, covering its clinical symptoms, pathophysiology, genetics, and management. PJS also raises the risk of getting many malignancies, especially gastrointestinal and pelvic cancers. Symptoms of the gastrointestinal tract brought on by hamartomatous polyps are frequent and include stool blockage, bleeding, and stomach pain. The pigmentation commonly appears as prominent bluish-black macules and frequently affects the skin and mucous membranes. Small macules and large regions of lentiginous pigmentation are both possible. Numerous areas, including the perioral area, buccal mucosa, fingers, and lips, exhibit pigmentation. Bowel obstruction and intussusception risk can be decreased by early identification and routine surveillance of gastrointestinal polyps. The gene serine/threonine kinase 11 (STK11) controls several biological functions, including cell polarity, growth, and proliferation. Genetic counseling is recommended for the affected individuals and their families. This can help assess the risk of passing on the condition to future generations and provide information about available reproductive options. Regular surveillance is crucial for managing the syndrome and reducing the risk of cancer development. Other syndromes and extra-gastrointestinal characteristics, such as somatic tumor polyps outside the gastrointestinal tract, are also linked to this syndrome.

Could Capsule Endoscopy Be Useful in Detection of Suspected Small Bowel Bleeding and IBD-10 Years of Single Center Experience.

A retrospective study in patients who underwent video capsule endoscopy (VCE) between 2006 and 2016 was conducted in the Clinic for gastroenterology and Hepatology, University Clinical Center of Serbia. A total of 245 patients underwent VCE. In 198 patients the indication was obscure gastrointestinal bleeding (OGIB), with 92 patients having overt and the other 106 occult bleeding. The remaining 47 patients underwent VCE due to suspected small bowel (SB) disease (i.e., Von Hippel-Lindau syndrome, familial adenomatous polyposis, Peutz Jeghers syndrome, Crohn's disease, prolonged diarrhea, abdominal pain, congenital lymphangiectasia, protein-losing enteropathy, tumors, refractory celiac disease, etc.). VCE identified a source of bleeding in 38.9% of patients (in the obscure overt group in 48.9% of patients, and in the obscure occult group in 30.2% of patients). The most common findings were angiodysplasias, tumors, Meckel's diverticulum and Crohn's disease. In the smaller group of patients with an indication other than OGIB, 38.3% of patients had positive VCE findings. The most common indication is OGIB, and the best candidates are patients with overt bleeding; patients with IBD should be evaluated in this setting.

Two missense STK11 gene variations impaired LKB1/adenosine monophosphate-activated protein kinase signaling in Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS) is a rare hereditary neoplastic disorder mainly associated with serine/threonine kinase 11 (STK11/LKB1) gene mutations. Preimplantation genetic testing can protect a patient's offspring from mutated genes; however, some variations in this gene have been interpreted as variants of uncertain significance (VUS), which complicate reproductive decision-making in genetic counseling. To identify the pathogenicity of two missense variants and provide clinical guidance. Whole exome gene sequencing and Sanger sequencing were performed on the peripheral blood of patients with PJS treated at the Reproductive and Genetic Hospital of Citic-Xiangya. Software was employed to predict the protein structure, conservation, and pathogenicity of the two missense variation sites in patients with PJS. Additionally, plasmids were constructed and transfected into HeLa cells to observe cell growth. The differences in signal pathway expression between the variant group and the wild-type group were compared using western blot and immunohistochemistry. Statistical analysis was performed using one-way analysis of variance. P < 0.05 was considered statistically significant. We identified two missense STK11 gene VUS [c.889A>G (p.Arg297Gly) and c.733C>T (p.Leu245Phe)] in 9 unrelated PJS families who were seeking reproductive assistance. The two missense VUS were located in the catalytic domain of serine/threonine kinase, which is a key structure of the liver kinase B1 (LKB1) protein. In vitro experiments showed that the phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) at Thr172 and LKB1 at Ser428 were significantly higher in transfected variation-type cells than in wild-type cells. In addition, the two missense STK11 variants promoted the proliferation of HeLa cells. Subsequent immunohistochemical analysis showed that phosphorylated-AMPK (Thr172) expression was significantly lower in gastric, colonic, and uterine polyps from PJS patients with missense variations than in non-PJS patients. Our findings indicate that these two missense STK11 variants are likely pathogenic and inactivate the STK11 gene, causing it to lose its function of regulating downstream phosphorylated-AMPK (Thr172), which may lead to the development of PJS. The identification of the pathogenic mutations in these two clinically characterized PJS patients has been helpful in guiding them toward the most appropriate mode of pregnancy assistance. These two missense variants can be interpreted as likely pathogenic variants that mediated the onset of PJS in the two patients. These findings not only offer insights for clinical decision-making, but also serve as a foundation for further research and reanalysis of missense VUS in rare diseases.

Familial syndromes associated with testicular and paratesticular neoplasms: a comprehensive review.

A syndromic association between a subset of testicular/paratesticular neoplasms is well established. Such examples include Carney complex and large cell calcifying Sertoli cell tumor, Peutz-Jeghers syndrome and intratubular large cell hyalinizing Sertoli cell neoplasia, and VHL syndrome and clear cell papillary cystadenoma of the epididymis.However, recent studies proposed potential novel links between some testicular and paratesticular neoplasms with certain tumor syndromes. While more studies are still needed to solidify these associations, recent research suggests that a subset of Leydig cell tumors may arise in patients with hereditary leiomyomatosis and renal cell carcinoma syndrome or that some seminomas may occur in Lynch syndrome patients. Additionally, an association between testicular sex cord stromal tumors and paratesticular sarcomas with Familial adenomatous polyposis syndrome and DICER1 syndrome, respectively, has been proposed as well. This review provides a comprehensive overview of the intricate relationship between familial syndromes and associated testicular and paratesticular tumors, shedding light on their clinicopathological and molecular characteristics.

Imaging approaches for the diagnosis of genetic diseases affecting the female reproductive organs and beyond.

This review aims to provide an overview of neoplastic lesions associated with genetic diseases affecting the female reproductive organs. It seeks to enhance our understanding of the radiological aspects in diagnosing genetic diseases including hereditary breast and ovarian cancer syndromes, Lynch syndrome, Peutz-Jeghers syndrome, nevoid basal cell carcinoma syndrome, and Swyer syndrome, and explores the patterns and mechanisms of inheritance that require elucidation. Additionally, we discuss the imaging characteristics of lesions occurring in other regions due to the same genetic diseases.

Clinical and Molecular Analysis in Patients with Peutz-Jeghers Syndrome.

Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder linked to increased cancer risk due to specific genetic variants in the STK11 gene. This study aimed to assess disease manifestations, genetic profiles, and genotype-phenotype correlations in PJS patients. Twenty patients from 14 families with PJS who were followed up at our clinic between 2011 and 2021 were included. Genetic susceptibility to hereditary cancers was assess-ed using targeted next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) of the STK11 gene. Clinical data were also collected and analyzed in conjunction with the genetic findings. Initial symptoms appeared around 18.9 years, predominantly abdominal pain and intussusception. Mucocutaneous lesions were found in 85%, and hamartomatous polyps in 90%. Dysplastic polyps were found in 4 patients, with 3 cases of malignancy. Nextgeneration sequencing identified 11 pathogenic and 3 likely pathogenic mutations, including 3 novel STK11 variants (LRG_319: c.598- 8_601del, LRG_319: c.708_718del, and LRG_319: c.146_147del). Next-generation sequencing diagnostic rate was 78.5% (11/14), and the overall diagnostic rate with NGS and MLPA studies was 85.7% (12/14). Patients without STK11 mutations had later symptom onset and potentially lower cancer risk. Truncated mutations are associated with earlier symptoms and elevated cancer risk. This is the first PJS case series in Turkey using the NGS and MLPA methods. It reports 3 novel mutations and emphasizes the genotype-phenotype relationship of PJS. With further studies, the genotype-phenotype relationship of STK11 variants will be better understood.

A case of Peutz-Jeghers syndrome presenting as multiple intussusception of small bowel – A rare surgical emergency

Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic disorder characterised by melanin pigment spots on the oral mucosa, lips, nasal alae, palm and soles, as well as hamartomatous polyps in the alimentary canal. Polyps are often a cause of intussusception in the affected patients. Cancers of the gastrointestinal system, uterus, and breast are common in patients with PJS. Long-term follow-up is required to prevent intussusception in children and cancer in adults. We report a classical case of PJS presenting with multiple intussusception of the small bowel in a 20-year-old male patient.

Progress report: Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is a rare, autosomal dominant polyposis syndrome. Presenting with a remarkable phenotype including development of characteristic gastrointestinal polyps, mucocutaneous pigmentations, and an increased risk of cancer, the syndrome has been subject to many studies concerning the natural course of disease. In most patients, pathogenic germline variants are detected in the STK11 gene including cases of mosaicism and structural variants. Yet, studies assessing the effect of surveillance, understanding of cancer development, as well as clinical studies evaluating chemoprevention are lacking. In addition, the impact of Peutz-Jeghers syndrome on mental health, education, and family planning are insufficiently addressed. In this progress report, we describe current knowledge, clinical phenotype, surveillance strategies, and future areas of research.

Gastric-type glandular lesions of the female genital tract excluding the cervix: emerging pathological entities.

In the last two decades or so, a spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation has been described, with gastric-type adenocarcinoma representing the most common human papillomavirus (HPV)-independent cervical adenocarcinoma. More recently, limited literature has reported a variety of gastric-type glandular lesions at other sites within the female genital tract and, as in the cervix (the most common site for these lesions), a spectrum of benign, premalignant and malignant lesions has been proposed. We provide an update and review of the emerging spectrum of gastric-type glandular lesions at female genital tract sites other than the cervix. In the endometrium, putative gastric-type glandular lesions include mucinous metaplasia of gastric-type, atypical mucinous proliferation of gastric-type and gastric-type adenocarcinoma. Similarly in the vagina, gastric-type adenosis, atypical adenosis and adenocarcinoma have been described. There have also been occasional reports of gastric-type lesions involving the ovary and fallopian tube. We provide guidance on how to recognise gastric-type lesions morphologically and immunophenotypically and stress that sometimes these lesions occur at more than one site within the female genital tract (synchronous/multifocal gastric-type lesions of the female genital tract), sometimes in association with Peutz-Jeghers syndrome.

C.290+1G&gt;A Mutation of the STK11 Gene Concerning Splicing Site in a Family with Peutz-Jeghers Syndrome

Синдром Пейтца-Егерса — редкое наследственное заболевание с аутосомно-доминантным типом наследования, которое обусловлено наличием патогенного варианта в гене STK11 (Serine-Threonine Kinase 11). Проведен молекулярно-генетический анализ, анализ родословной и клинических характеристик пациента с СПЕ. У 25-летней пациентки с клиническими признаками СПЕ выявлена замена c.290+1G&gt;A в гетерозиготном состоянии, которая затрагивает донорский сайт сплайсинга в 1 интроне гена STK11. Данный вариант определен у других членов семьи, у которых обнаружены полипы в кишечнике и пятна на коже и слизистой рта. У папы, бабушки, тети пробанда были диагностированы онкологические заболевания, включая рак тонкой кишки, рак легких, рак шейки матки.

Peutz–Jeghers syndrome with polyps in the stomach, duodenum, and small and large intestine: a case report

BackgroundPeutz–Jeghers syndrome is a rare hereditary condition characterized by gastrointestinal polyps and pigmented oral lesions. The case contributes to a deeper understanding of Peutz–Jeghers syndrome and underscores the significance of interdisciplinary collaboration for accurate diagnosis and tailored therapeutic strategies.Case descriptionWe present a case of a 15-year-old Afghan female patient with multiple polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. Despite previous medical visits and colonoscopies, her symptoms persisted. A multidisciplinary team discussed the case and recommended further investigations and interventions. A polypectomy was performed, confirming the presence of hamartomatous polyps. The patient was diagnosed with Peutz–Jeghers syndrome, but during the course of treatment she went through complications and was managed surgically as well.ConclusionTimely polyp removal and lifelong surveillance are crucial in managing Peutz–Jeghers syndrome. Further research and genetic analysis are needed to improve understanding and management of this rare disorder.

How to do a laparoscopic-assisted endoscopic 'clean sweep' for small bowel polyp clearance in Peutz Jeghers syndrome.

We demonstrate the technical details of laparoscopic-assisted endoscopic 'clean sweep' for small bowel polyp clearance in Peutz Jeghers Syndrome. A 'clean sweep' reduces the risk for future recurrences but was previously performed with an open technique. A minimally invasive approach is safe, reduces bowel trauma and has good postoperative outcomes.

Preoperative multimodal ultrasonic imaging in a case of Peutz-Jeghers syndrome complicated by atypical lobular endocervical glandular hyperplasia: a case report and literature review

BackgroundPeutz-Jeghers syndrome (PJS), an autosomal dominant multiple cancerous disorder, is clinically characterized by mucocutaneous macules and multiple gastrointestinal hamartomatous polyps. Gastric-type endocervical adenocarcinoma (G-EAC), a special subtype of cervical adenocarcinoma with non-specific symptoms and signs, is known to occur in approximately 11% of female patients with PJS.Case presentationHere, we report a case of PJS in a 24-year-old female with multiple mucocutaneous black macules who complained of vaginal discharge and menorrhagia. Moreover, we first described the multimodal ultrasonographical manifestations of PJS-correlated G-EAC. The three-dimensional reconstructed view of G-EAC on 3D realisticVue exhibited a distinctive “cosmos pattern” resembling features on magnetic resonance imaging, and the contrast-enhanced ultrasound displayed a “quick-up and slow-down” pattern of the solid components inside the mixed cervical echoes. We reported the multimodal ultrasonographical characteristics of a case of PJS-related G-EAC, as well as reviewed PJS-related literature and medical imaging features and clinical characteristics of G-EAC to provide insight into the feasibility and potential of utilizing multimodal ultrasonography for the diagnosis of G-EAC.ConclusionsMultimodal ultrasound can visualize morphological features, solid components inside, and blood supplies of the G-EAC lesion and distinguish the G-EAC lesion from normal adjacent tissues. This facilitates preoperative diagnosis and staging of PJS-related G-EAC, thereby aiding subsequent health and reproductive management for patients with PJS.

Cellular and molecular characteristics of stromal Lkb1 deficiency-induced gastrointestinal polyposis based on single-cell RNA sequencing.

Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (Stk11), is a serine/threonine kinase and tumor suppressor that is strongly implicated in Peutz-Jeghers syndrome (PJS). Numerous studies have shown that mesenchymal-specific Lkb1 is sufficient for the development of PJS-like polyps in mice. However, the cellular origin and components of these Lkb1-associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen-inducible Lkb1flox/flox;Myh11-Cre/ERT2 and Lkb1flox/flox;PDGFRα-Cre/ERT2 mice, performed single-cell RNA sequencing (scRNA-seq) and imaging-based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS. We found that Lkb1flox/+;Myh11-Cre/ERT2 mice developed gastrointestinal polyps starting at 9 months after tamoxifen treatment. scRNA-seq revealed aberrant stem cell-like characteristics of epithelial cells from polyp tissues of Lkb1flox/+;Myh11-Cre/ERT2 mice. The Lkb1-associated polyps were further characterized by a branching smooth muscle core, abundant extracellular matrix deposition, and high immune cell infiltration. In addition, the Spp1-Cd44 or Spp1-Itga8/Itgb1 axes were identified as important interactions among epithelial, mesenchymal, and immune compartments in Lkb1-associated polyps. These characteristics of gastrointestinal polyps were also demonstrated in another mouse model, tamoxifen-inducible Lkb1flox/flox;PDGFRα-Cre/ERT2 mice, which developed obvious gastrointestinal polyps as early as 2-3 months after tamoxifen treatment. Our findings further confirm the critical role of mesenchymal Lkb1/Stk11 in gastrointestinal polyposis and provide novel insight into the cellular complexity of Lkb1-associated polyp biology. © 2024 The Pathological Society of Great Britain and Ireland.

Exploring the histogenesis of STK11 adnexal tumour using electron microscopy.

STK11 adnexal tumour is a recently described female genital tract tumour, usually identified in a paratubal location, often associated with Peutz-Jeghers syndrome (PJS) and with STK11 gene alterations identified in most of the cases. Morphologically, this tumour is composed of cells arranged in a variety of patterns, including cords, trabeculae, tubules and cystic and acinar structures. The cells are only moderately pleomorphic and mitotic activity is variable. As tumour cells express epithelial, sex cord stromal and mesothelial markers, STK11 adnexal tumour may be of sex cord stromal, epithelial or mesothelial origin; a Wolffian origin has also been suggested. We report the ultrastructural features of two STK11 adnexal tumours and compare their ultrastructural features with those of other sex cord stromal tumours, a granulosa cell tumour cell line, as well as the known ultrastructural features of epithelial, mesothelial and Wolffian cells. On ultrastructural examination, two STK11 adnexal tumours showed an admixture of elongated cells with regular elongated nuclei and polygonal cells with nuclei showing markedly irregular outlines and prominent nucleoli. Extracellular collagen fibres were identified. These are common ultrastructural features of sex cord stromal tumours, principally sex cord tumour with annular tubules; no ultrastructural features of epithelial, mesothelial or Wolffian cells were found. These findings in conjunction with the shared clinical and genetic association with PJS and shared molecular changes in STK11 gene suggest that STK11 adnexal tumour represents a poorly differentiated sex cord tumour.

Differential Diagnoses and Management Approaches for Gastric Polyposis

Multiple gastric polyps are observed in various polyposis syndromes and conditions associated with polypoid lesion development in the stomach. Polyposis syndromes often occur concurrently with specific malignant tumors and can manifest at any point in an individual’s lifespan, thus explaining the diversity in surveillance methods. Furthermore, genetic counseling and surveillance are essential not only for the patients themselves but also for their blood relatives. Therefore, the accurate diagnosis and appropriate surveillance of multiple gastric polyps are crucial for improving patient outcomes. This review aims to provide essential information on such lesions along with representative endoscopic images of familial adenomatous polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Cronkhite-Canada syndrome, juvenile polyposis syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, neuroendocrine tumors in autoimmune gastritis, proton pump inhibitor-related gastric mucosal changes, and multiple submucosal heterotopic glands. We wish for this review to serve as a valuable resource for endoscopists seeking to deepen their comprehension of gastric polyposis.