Peutz-Jeghers Research Articles

Bladder hamartoma in Peutz-Jeghers syndrome: a rare case report

BackgroundPeutz-Jeghers syndrome is an autosomal dominant disease characterized by mucocutaneous pigmentation and hamartomatous polyps in the gastrointestinal tract (GIT). There have also been cases of extra GIT polyps such as the renal pelvis, urinary bladder, lungs and nares. Bladder hamartoma is an extremely rare finding, with only 12 cases described in the literature up to now. The rarity of the condition necessitates a comprehensive compilation of managements up to now so as to provide a better tool for the treatment of such conditions in the future.Case presentationA twenty-year-old male, known to have Peutz-Jeghers syndrome, presented to us complaining of obstructive urinary symptoms. A urethrogram done showed a filling defect at the base of the urinary bladder. The mass was resected transurethrally, and histopathology revealed a hamartoma of the bladder. The patient has since remained tumor-free on follow-up.ConclusionsTransurethral resection of the bladder mass proved to be an effective therapy in this patient with no recurrence on the patient’s follow-up till now. There is still, however, a dearth of knowledge regarding the management of bladder hamartomas owing to the extreme rarity of the case.

Peutz–Jeghers' syndrome in pediatric dermatological practice

Peutz–Jeghers' syndrome is a rare hereditary disease inherited by an autosomal dominant type, manifested by a characteristic clinical picture of skin lesions and hamartomas of the gastrointestinal tract. Complications of the disease include bleeding from polyps, anemia, intussusception and intestinal necrosis, as well as a high likelihood of developing malignant tumors. For the first time the syndrome was described at the beginning of the last century, and it is of interest to dermatologists, gastroenterologists, oncologists and surgeons due to the clinical heterogeneity of intestinal and skin manifestations. The article describes a clinical case of a 5-year-old girl with the Peutz–Jaegers syndrome. The patient complained of periodic dull abdominal pain that worsened after eating solid food. During the examination of the skin and mucous membranes the doctors discovered rashes on the face: perioral area, on the red border of the lips and on the mucous membrane of the lips, inside the cheeks, hard palate. Esophagogastroduodenoscopy (EGDS) revealed a polyp on a pedicle in the prepyloric part – it was removed during repeated EGDS under endotracheal anesthesia. Fibrocolonoscopy revealed hyperpigmentation of the dome of the cecum. To confirm the diagnosis, the doctors carried out DNA testing which found a mutation of the STK11 gene. Pigmentation of the perioral area is an early symptom of Peutz–Jeghers' syndrome suggesting optimal examination. Early recognition of the syndrome in children is important in the context of reducing the risk of developing intestinal obstruction, bleeding, and cancer complications in the future.

Peutz-Jeghers Syndrome Presented as Jejunojejunal Intussusception

Peutz-Jeghers Syndrome Presented as Jejunojejunal Intussusception

Inhibition of β-Catenin Activity Abolishes LKB1 Loss-Driven Pancreatic Cystadenoma in Mice.

Pancreatic cancer (PC) is the seventh leading cause of cancer death worldwide, and remains one of our most recalcitrant and dismal diseases. In contrast to many other malignancies, there has not been a significant improvement in patient survival over the past decade. Despite advances in our understanding of the genetic alterations associated with this disease, an incomplete understanding of the underlying biology and lack of suitable animal models have hampered efforts to develop more effective therapies. LKB1 is a tumor suppressor that functions as a primary upstream kinase of adenine monophosphate-activated protein kinase (AMPK), which is an important mediator in the regulation of cell growth and epithelial polarity pathways. LKB1 is mutated in a significant number of Peutz–Jeghers syndrome (PJS) patients and in a small proportion of sporadic cancers, including PC; however, little is known about how LKB1 loss contributes to PC development. Here, we report that a reduction in Wnt/β-catenin activity is associated with LKB1 tumor-suppressive properties in PC. Remarkably, in vivo functional analyses of β-catenin in the Pdx-1-Cre LKB1L/L β-cateninL/L mouse model compared to LKB1 loss-driven cystadenoma demonstrate that the loss of β-catenin impairs cystadenoma development in the pancreas of Pdx-1Cre LKB1L/L mice and dramatically restores the normal development and functions of the pancreas. This study further determined the in vivo and in vitro therapeutic efficacy of the β-catenin inhibitor FH535 in suppressing LKB1 loss-driven cystadenoma and reducing PC progression that delineates the potential roles of Wnt/β-catenin signaling in PC harboring LKB1 deficiency.

Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations.

The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include adenomas and hamartomas, may arise sporadically or be associated with hereditary tumor syndromes, such as familial adenomatous polyposis, MUTYH-associated polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. In addition, dysplastic, preinvasive lesions have been observed adjacent to small bowel adenocarcinomas complicating immune-related disorders, such as celiac or Crohn’s disease. Adenomatous lesions may exhibit an intestinal-type, gastric-type, or, very rarely, serrated differentiation, related to different molecular pathogenetic mechanisms. Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn’s disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions.

Sex cord tumor with annular tubules of ovary- An unusual case report

Sex cord tumor with annular tubules (SCTAT) accounts for approximately 2.3% of Sex cord stromal tumor (SCST) and is a relatively infrequently encountered, distinctive type of ovarian neoplasm. SCTAT is most commonly seen in females of reproductive age group. Peutz-Jeghers syndrome (PJS) may be associated with SCTAT in one-third of the patients. A 23 year old unmarried female presented with pain abdomen and mass per abdomen. Ultrasonography revealed a left adnexal mass. Considering clinical presentation and radiological findings, a differential diagnosis of teratoma/ dysgerminoma was given. Intraoperatively, a large left ovarian mass was noted. The mass was excised and sent for histopathology study. On microscopy, diagnosis of SCTAT was rendered. SCTAT are uncommon tumors with unique morphologic pattern. Our case was a non-syndromic case with no other features of PJS. Since 15-20% of non-syndromic cases can have a malignant course later in life, a long term follow up is required. Key message: Ovarian tumors at young age like SCTAT are very important to diagnose accurately as patient’s prognosis has to be weighed against preserving fertility and these tumors should be followed up for a long period. Keywords: Ovarian tumor, Peutz-Jeghers syndrome, Reproductive age group.

Histologic heterogeneity and syndromic associations of non-ampullary duodenal polyps and superficial mucosal lesions

BackgroundDuodenal polyps and superficial mucosal lesions (DP/SMLs) are poorly characterised. AimsTo describe a series of endoscopically-diagnosed extra-ampullary DPs/SMLs. MethodsThis is a retrospective study conducted in a tertiary referral Endoscopy Unit, including patients who had DPs or SMLs that were biopsied or removed in 2010–2019. Age, gender, history of familial polyposis syndromes, DP/SML characteristics were recorded. Histopathological, immunohistochemical and molecular analyses were performed. Results399 non-ampullary DP/SMLs from 345 patients (60.6% males; median age 67 years) were identified. Gastric foveolar metaplasia represented the most frequent histotype (193 cases, 48.4%), followed by duodenal adenomas (DAs; 77 cases, 19.3%). Most DAs (median size 6 mm) were sessile (Paris Is; 48%), intestinal-type (96.1%) with low-grade dysplasia (93.5%). Among syndromic DAs (23%), 15 lesions occurred in familial adenomatous polyposis 1, two were in MUTYH-associated polyposis and one was in Peutz-Jeghers syndrome (foveolar-type, p53-positive, low-grade dysplasia). Only one (3.3%) tubular, low-grade DA showed mismatch repair deficiency (combined loss of MLH1 and PMS2, heterogeneous MSH6 expression), and it was associated with a MLH1 gene germline mutation (Lynch syndrome). ConclusionDPs/SMLs are heterogeneous lesions, most of which showing foveolar metaplasia, followed by low-grade, intestinal-type, non-syndromic DAs. MMR-d testing may identify cases associated with Lynch syndrome.

Successful treatment of oral pigmented spots in Chinese subjects with Peutz-Jeghers syndrome using a 755-nm picosecond laser

Successful treatment of oral pigmented spots in Chinese subjects with Peutz-Jeghers syndrome using a 755-nm picosecond laser

Polipose gástrica: relato de caso e revisão da literatura

Pólipos gastrointestinais são elevações da mucosa circundante do sistema digestório, encontradas frequentemente em exames endoscópicos de rotina. A grande maioria é achado acidental e alguns pólipos podem indicar doença ou síndrome associada. Este artigo tem como objetivo apresentar um caso de polipose gástrica manifestada como Síndrome de Peütz-Jeghers em uma paciente de 25 anos, do sexo feminino, com história de dor abdominal em região epigástrica há 12 dias da admissão hospitalar, que evoluiu com vômitos e hematêmese 3 dias antes do internamento. A paciente realizou endoscopia digestiva alta (EDA), que evidenciou múltiplas lesões polipoides, regulares e de superfície lisa. Tomografia computadorizada (TC) do abdômen visualizou volumosa lesão vegetante coraliforme, de 16,3 x 10,2 x 5,4cm. Optou-se por realizar uma gastrectomia total com reconstrução em Y-de-Roux. O tempo total da cirurgia foi de 150min e ocorreu sem complicações. Paciente evoluiu com boas condições clínicas, sem intercorrências e recebeu alta hospitalar no 9º dia de pós-operatório (DPO). Estudo histopatológico da peça cirúrgica (estômago) evidenciou múltiplos pólipos gástricos de padrão predominante hamartomatoso, com transformação adenomatosa focal, margens cirúrgicas livres, sugerindo síndrome de Peütz-Jeghers. Nossa paciente não demonstrou hiperpigmentação mucocutânea, corroborando o fato de que a hiperpigmentação não é condição “sine qua non” para a síndrome de Peütz-Jeghers.

A Rare Cause of Intestinal Obstruction in Paediatric Patients

Peutz-Jeghers syndrome is an autosomal dominant hamartomatous polyposis involving gastrointestinal tract associated with mucocutaneous hyperpigmentation involving lips, buccal mucosa ,hand and feet and predisposing the patient to various extraintestinal and intestinal cancers.This article includes case report of a 12 year female diagnosed with intussusception due to Peutz-JeghersSyndrome. This patient underwent emergency exploratory laparotomy followed by resection of about 30 cm necrosed , gangrenous ileum about 50cm proximal to ileocecal junction and then ileoileal anastomosis performed . This patient had pigmented hypermelanotic macules over lower lip ,buccal mucosa and face. This case was thoroughly examined and found to be a rare case of intestinal obstruction in paediatric patients. Key words: Peutz Jeghers syndrome; intussusception; hamartomatous polyposis

Utility of Simethicone as a Terminal Adjunct to Standard Bowel Preparation for Colonoscopies – A Retrospective Cohort Study

Peutz-Jeghers syndrome is an autosomal dominant hamartomatous polyposis involving gastrointestinal tract associated with mucocutaneous hyperpigmentation involving lips, buccal mucosa ,hand and feet and predisposing the patient to various extraintestinal and intestinal cancers.This article includes case report of a 12 year female diagnosed with intussusception due to Peutz-Jeghers Syndrome. This patient underwent emergency exploratory laparotomy followed by resection of about 30 cm necrosed , gangrenous ileum about 50cm proximal to ileocecal junction and then ileoileal anastomosis performed . This patient had pigmented hypermelanotic macules over lower lip ,buccal mucosa and face. This case was thoroughly examined and found to be a rare case of intestinal obstruction in paediatric patients. Key words: Peutz-Jeghers-syndrome; intussusception; hamartomatous polyposis.

Solitary hamartomatous duodenal polyp in an infant

Abstract Duodenal polyps are uncommon. They are usually syndromic seen commonly with Familial adenomatosis polyposis or Peutz-Jegher's syndrome, but maybe seen as a solitary non-syndromic polyp presenting with gastrointestinal symptoms. Few cases of Solitary duodenal hamartomatous polyps have been seen in adults, but to the best of our knowledge never in an infant. We hereby report a case of a 6week old infant who presented with bilious vomiting, weight loss and dehydration. Radiological investigations revealed an obstructive duodenal polyp. Duodenotomy and excision proved curative.

Ileoileal intussusception treated by polypectomy with spiral enteroscopy in Peutz-Jeghers syndrome.

Ileoileal intussusception treated by polypectomy with spiral enteroscopy in Peutz-Jeghers syndrome.

Esophageal Cancer: An Updated Review.

The incidence of esophageal cancer (EC) is on the rise. With the distinct subtypes of adenocarcinoma and squamous cell carcinoma comes specific risk factors, and as a result, people of certain regions of the world can be more prone to a subtype. For example, squamous cell carcinoma of the esophagus has the highest incidence in eastern Africa and eastern Asia, with smoking being a major risk factor, whereas adenocarcinoma is more prevalent in North America and western Europe, with gastroesophageal reflux disease being a leading risk factor. With that being said, adenocarcinoma and squamous cell carcinoma have similar and unfortunately poor survival rates, partly because EC is prone to early metastasis given that the esophagus does not have a serosa, as well as the superficial nature of its lymphatics compared with the rest of the gastrointestinal tract. This makes early detection of the utmost importance, and certain patients have been shown to have the benefit of screening/surveillance endoscopies, including those with Barrett's esophagus, lye-induced/caustic strictures, tylosis, and Peutz-Jeghers syndrome. Until treatments significantly improve, identifying EC at the earliest stage will have the best success for patient outcomes, and further elucidation of its pathogenesis and risk factors may lead to identifying other high-risk groups that should be screened.

56371 The Signaling Axis of Tumor Suppressor LKB1 in Triple Negative Breast Cancer

ABSTRACT IMPACT: Identifying an important pathway in treatment resistant TNBC will allow for the future development of clinical therapeutics specific for this disease. OBJECTIVES/GOALS: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer characterized by negative expression of estrogen receptor, progesterone receptor, and HER2/neu amplification. It resists therapies and has a high recurrence rate after resection. The goal of my research is to identify & characterize a TNBC pathway for future development of therapies. METHODS/STUDY POPULATION: The project uses a combination of cell lines, patient derived xenograft (PDX) models, as well as patient databases. Standard cellular and molecular biology techniques will be used including: Cell culture, qPCR, western blotting, and flow cytometry. RESULTS/ANTICIPATED RESULTS: LKB1 is a master kinase that activates 14 possible downstream kinases. The signaling pathway has been demonstrated to play a role in energy homeostasis and metabolism. Mutation of LKB1 signaling results in Peutz-Jeghers Syndrome and is associated with neoplasias of the lung, pancreas, and breast. Based on preliminary analysis, overexpression of LKB1 by shRNA in TNBC cell lines results in suppression of EMT and reduction of the cancer stem cell population. Additional studies show that LKB1 overexpression has no effect on growth rate in 2D culture while significant reduction in 3D mammosphere formations can be seen. Downstream studies using commercially available SIK1 inhibitor HG-9-91-01 is able to induce a larger fraction of CSC from reduced LKB1 overexpression as well as from baseline levels. DISCUSSION/SIGNIFICANCE OF FINDINGS: Overall, our results suggest that LKB1 acts through SIK1 to suppress EMT and the generation of cancer stem cells. This results in reduced cancer functionality, as evidenced by inhibition of mammosphere formation. These results establishes a foundation for future mechanistic studies on the LKB1 axis and its mechanisms in TNBC.

Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is a rare, autosomal dominant, hereditary polyposis syndrome defined by gastrointestinal hamartomas and mucocutaneous pigmentations, caused by a germline mutation in the serine/ threonine kinase 11 or liver kinase B1 (STK11/LKB1) genes. Hamartomatous polyps located throughout the gastrointestinal tract can be complicated by bleeding and small bowel intussusception, potentially leading to the need for emergency surgery. Individuals suffering from Peutz-Jeghers syndrome have an increased lifetime risk of various forms of cancer (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular). Surveillance should lead to the prevention of complications and thus a reduction in mortality and morbidity of patients. A combined approach based on wireless capsule endoscopy, magnetic resonance enterography and device-assisted enteroscopy is effective in reduction of the polyp burden and thus decreasing the risk of bleeding and intussusception. Current guidelines for screening and surveillance are mostly based on expert opinion rather than evidence. Peutz-Jeghers syndrome is an emerging disease that significantly affects the quality of life enjoyed by patients. Despite of all the progress in improved early diagnostics, options for advanced endoscopic therapy and elaborate surveillance, acute and chronic complications decrease the life expectancy of patients suffering from Peutz-Jeghers syndrome.

The Role of Genetic Mutations in the Prevention of Malignant Tumours in a Healthy Population (A Review)

The prevention of malignant neoplasms in a healthy population is a priority task of national healthcare systems. Population screening and genetic counselling programmes allow identification of not only precancerous conditions, but also a genetic susceptibility to tumour diseases. Most hereditary cancers are passed on following an autosomal dominant pattern. Timely screening in healthy individuals, who may be potential carriers of mutated genes, facilitates the development of personalized preventive measures. The history of breast and/or ovarian cancer in close relatives is an important factor in early detection of genetic mutations in healthy patients, both women and men. The history of breast, ovarian or prostate cancer in close relatives increases significantly the chances of detecting a germinal mutation in the BRCA1 and BRCA2 genes in a proband. Genes associated with an increased risk of developing pancreatic cancer are BRCA1, BRCA2, CDKN2A, PALB2, PRSS1 and STK11. The most common syndromes of genetic mutations increasing the risk of cancer development include hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial adenomatous polyposis, Peutz—Jeghers syndrome and Lee­Fraumeni syndrome, multiple endocrine neoplasia syndrome.

A Distinctive Adnexal (Usually Paratubal) Neoplasm Often Associated With Peutz-Jeghers Syndrome and Characterized by STK11 Alterations (STK11 Adnexal Tumor): A Report of 22 Cases.

We describe 22 examples of a novel, usually paratubal, adnexal tumor associated with Peutz-Jeghers syndrome in nearly 50% of cases that harbored STK11 alterations in all tested (n=21). The patients ranged from 17 to 66 years (median=39 y) and the tumors from 4.5 to 25.5 cm (median=11 cm). Most (n=18) were paratubal, with metastases noted in 11/22 (50%) and recurrences in 12/15 (80%). Morphologically, they were characterized by interanastomosing cords and trabeculae of predominantly epithelioid cells, set in a variably prominent myxoid to focally edematous stroma, that often merged to form tubular, cystic, cribriform, and microacinar formations, reminiscent of salivary gland-type tumors. The tumor cells were uniformly atypical, often with prominent nucleoli and a variable mitotic index (median=9/10 HPFs). The tumors were usually positive to a variable extent for epithelial (CAM5.2, AE1/AE3, cytokeratin 7), sex cord (calretinin, inhibin, WT1), and mesothelial (calretinin, D2-40) markers, as well as hormone receptors. PAX8, SF1, and GATA-3 were rarely positive, while claudin-4, FOXL2, and TTF-1 were consistently negative. All sequenced tumors (n=21) harbored alterations in STK11, often with a loss of heterozygosity event. There were no other recurrently mutated genes. Recurrent copy number alterations included loss of 1p and 11q, and gain of 1q, 15q, and 15p. Despite an extensive morphologic, immunohistochemical, and molecular evaluation, we are unable to determine with certainty the histogenesis of this unique tumor. Wolffian, sex cord stromal, epithelial, and mesothelial origins were considered. We propose the term STK11 adnexal tumor to describe this novel entity and emphasize the importance of genetic counseling in these patients as a significant number of neoplasms occur in association with Peutz-Jeghers syndrome.

The Management of Peutz-Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline.

The scientific data to guide the management of Peutz–Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when ≥80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated.

Laparoscopic-assisted disinvagination and polypectomy for multiple intussusceptions induced by small intestinal polyps in patients with Peutz-Jeghers syndrome: a case report

BackgroundPeutz–Jeghers syndrome (PJS) is a very rare autosomal dominant genetic disorder characterized by hamartomatous polyps in the gastrointestinal tract and hyperpigmentation of the lips, hands, and feet. The hamartomatous polyps in the small intestine often cause intussusception and bleeding.Case presentationA 62-year-old male was hospitalized for treatment of deep vein thrombosis and pulmonary embolism. In the small intestine, computed tomography showed three small polyps with intussusceptions. Since the patient had gastrointestinal polyposis and pigmentation of his lips, fingers, and toes, he was diagnosed with PJS. After an inferior vena cava filter was placed, he underwent laparoscopic-assisted surgery. The polyps causing intussusception were resected as far as possible without intestinal resection, since they had caused progressive anemia and might cause intestinal obstruction in the future. The patient was discharged from the hospital on postoperative day 9 without complications.ConclusionsLaparoscopic-assisted disinvagination and polypectomy is a useful, minimally invasive treatment for multiple intussusceptions caused by small intestinal polyps in patients with PJS.