Two Types of Polyp Shape Observed in the Stomach of Patients with Peutz-Jeghers Syndrome.

The characteristics of gastric polyps in patients with Peutz-Jeghers (PJ) syndrome (PJS) have not been fully investigated. The objective of this study was to reveal the endoscopic and pathologic findings of gastric polyps in patients with PJS. We reviewed 11 patients with PJS treated at 6 institutions, and summarized the endo-scopic and pathologic features of their gastric polyps. The polyps were mainly classified into 2 types: (i) soli-tary or sporadic polyps > 5 mm, reddish in color with a sessile or semi-pedunculated morphology (n = 9); and (ii) multiple sessile polyps ≤ 5 mm with the same color tone as the peripheral mucosa (n = 9). Patients who underwent endoscopic mucosal resection for polyps > 5 mm were diagnosed with PJ polyps (n = 2), whereas those who underwent biopsy were diagnosed with hyperplastic polyps. Polyps ≤ 5 mm were pathologically diagnosed as fundic gland polyps or hyperplastic polyps. This study revealed that patients with PJS present with 2 types of polyps in the stomach. Endoscopic mucosal resection of polyps > 5 mm seems necessary for the pathologic diagnosis of PJ polyps.

Chronic abdominal pain and diarrhea.

Pigmented macules on the patient's oral mucosa provided an important clue to the diagnosis.

Extra-ampullary Peutz-Jeghers polyp causing duodenal intussusception leading to biliary obstruction: a case report.

BACKGROUND: Duodenal Peutz-Jeghers polyp is a rare cause of duodenal or biliary obstruction. However, a sporadic Peutz-Jeghers polyp leading to simultaneous biliary and duodenal obstruction has not been reported. CASE PRESENTATION: We report a case of a 25-year-old Sri Lankan woman presenting with features of recurrent upper small intestinal obstruction and biliary obstruction. She had clinical as well as biochemical evidence of intermittent biliary obstruction. Evidence of duodenal intussusception was found in a computed tomography enterogram and a duodenal polyp was noted as the lead point. Marked elongation and distortion of her lower common bile duct with intrahepatic duct dilatation was also noted and the ampulla was found to be on the left side of the midline pulled toward the intussusceptum. Open polypectomy and reduction of intussusception were done and she became fully asymptomatic following surgery. Histology of the resected specimen was reported as a typical "Peutz-Jeghers polyp". As there was not enough evidence to diagnose Peutz-Jeghers syndrome this was considered to be a sporadic Peutz-Jeghers polyp. CONCLUSION: Rare benign causes such as a duodenal polyp should be considered and looked for in initial imaging, when the cause for concurrent biliary and intestinal obstruction is uncertain, particularly in young individuals.

Sex cord tumor with annular tubules: an incidental finding in an endometriotic cyst--the first known cooccurrence.

Sex cord tumor with annular tubules (SCTATs) is a relatively rare ovarian neoplasm often having a syndromic association with Peutz-Jeghers syndrome (PJS). Other associations described with this rare neoplasm include adenoma malignum of cervix, Turners syndrome, dysgerminoma, gonadoblastoma, endometrial carcinoma, and endometriosis of fallopian tube. We describe for the first time to the best of our literature search the incidental detection of SCTAT coexisting with an endometriotic cyst of ovary. Meticulous histological scanning and awareness is mandatory for detection of such unusual incidental lesions. Non-PJS SCTATs tend to be larger and could be more prone to distant metastasis, warranting subsequent follow-up.

Hamartomatous polyposis syndromes: a review.

Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as Gorlin Syndrome and multiple endocrine neoplasia syndrome 2B are sometimes referred to as HPS. HPS is characterized by the development of hamartomatous polyps in the gastrointestinal tract as well as several extra-intestinal findings such as dermatological and dysmorphic features or extra-intestinal cancer. The syndromes are rare and inherited in an autosomal dominant manner.The diagnosis of HPS has traditionally been based on clinical criteria, but can sometimes be difficult as the severity of symptoms range considerably from only a few symptoms to very severe cases - even within the same family. De novo cases are also frequent. However, because of the discovery of several associated germline-mutations as well as the rapid development in genetics it is now possible to use genetic testing more often in the diagnostic process. Management of the syndromes is different for each syndrome as extra-intestinal symptoms and types of cancers differs.Clinical awareness and early diagnosis of HPS is important, as affected patients and at-risk family members should be offered genetic counselling and surveillance. Surveillance in children with HPS might prevent or detect intestinal or extra-intestinal complications, whereas in adulthood surveillance is recommended due to an increased risk of cancer e.g. intestinal cancer or breast cancer.

Findings from the Peutz-Jeghers syndrome registry of uruguay.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients. METHODS: Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed. RESULTS AND DISCUSSION: 25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal polyps. 72% required urgent surgery due to intestinal obstruction. 3 families had multiple cases of seizure disorder, representing 20% of cases. 28% developed cancer and two patients had more than one cancer. An STK11 mutation was found in 8 of the 9 families analyzed. A unique M136K missense mutation was noted in one family. Comparing annual live births and PJS birth records from 1970 to 2009 yielded an incidence of 1 in 155,000. CONCLUSION: The Uruguayan Registry for Peutz-Jeghers patients showed a high chance of emergent surgery, epilepsy, cancer and shortened life expectancy. The M136K missense mutation is a newly reported STK 11 mutation.

Recurrent small intestine intussusception in a patient with Peutz-Jeghers syndrome / Invaginación recurrente del intestino delgado en un paciente con síndrome de Pentz-Jeghers

Peutz-Jeghers syndrome is a rare hereditary autosomal dominant disease caused by a mutation of the tumor suppressor gene serine/threonine kinase 11 located in chromosome 19p13.3. It is characterized by the presence of extensive mucocutaneous pigmentation, especially of the lips and the occurrence of hamartomatous polyps throughout the gastrointestinal tract. Gastrointestinal hamartomas occur predominantly in the small intestine and can become symptomatic leading usually to intestinal obstruction and abdominal pain. We present a case of recurrent intestinal obstruction caused by small bowel intussusception treated by reduction, enterotomy and polypectomy and followed by intraoperative enteroscopy and endoscopic polypectomy(AU)

Insights from model organisms on the functions of the tumor suppressor protein LKB1: zebrafish chips in.

The tumor suppressor LKB1 has emerged as a critical regulator of cell polarity and energy­metabolism. Studies in diverse model organisms continue to unravel the pathways downstream of LKB1; the emerging picture is that the outcomes of LKB1 signaling are mediated by a plethora of tissue­specific and context­dependent effectors.

LKB1 and AMPK family signaling: the intimate link between cell polarity and energy metabolism.

Research on the LKB1 tumor suppressor protein mutated in cancer-prone Peutz-Jeghers patients has continued at a feverish pace following exciting developments linking energy metabolism and cancer development. This review summarizes the current state of research on the LKB1 tumor suppressor. The weight of the evidence currently indicates an evolutionary conserved role for the protein in the regulation of various aspects of cellular polarity and energy metabolism. We focus on studies examining the concept that both cellular polarity and energy metabolism are regulated through the conserved LKB1-AMPK signal transduction pathway. Recent studies from a variety of model organisms have given new insight into the mechanism of polyp development and cancer formation in Peutz-Jeghers patients and the role of LKB1 mutation in sporadic tumorigenesis. Conditional LKB1 mouse models have outlined a tissue-dependent context for pathway activation and suggest that LKB1 may affect different AMPK isoforms independently. Elucidation of the molecular mechanism responsible for Peutz-Jeghers syndrome will undoubtedly reveal important insight into cancer development in the larger population.

Hamartomatous polyposis syndromes.

The hamartomatous polyposis syndromes are a heterogeneous group of disorders that share an autosomal-dominant pattern of inheritance and are characterized by hamartomatous polyps of the gastrointestinal tract. These syndromes include juvenile polyposis syndrome, Peutz-Jeghers syndrome and the PTEN hamartoma tumor syndrome. The frequency and location of the polyps vary considerably among syndromes, as does the affected patient's predisposition to the development of gastrointestinal and other malignancies. Although the syndromes are uncommon, it is important for the clinician to recognize these disorders because they are associated with considerable morbidity and mortality, not only from malignancy but also from nonmalignant manifestations such as bleeding, intussusception, and bowel obstruction. Each hamartomatous polyposis syndrome has its own distinctive organ-specific manifestations and each requires a different surveillance strategy, which makes accurate diagnosis crucial for appropriate patient management. The availability of clinical genetic testing for these disorders means that appropriate recognition allows for timely referral for cancer genetic counseling, and often allows for predicative testing in at-risk family members. Promisingly, an understanding of the molecular pathogenesis of these disorders offers insights into the mechanisms underlying the development of sporadic malignancy, and enables rational selection of targeted therapies that warrant further investigation.

The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division.

We have isolated lethal mutations in the Drosophila lkb1 gene (dlkb1), the homolog of C. elegans par-4 and human LKB1 (STK11), which is mutated in Peutz-Jeghers syndrome. We show that these mutations disrupt spindle formation, resulting in frequent polyploid cells in larval brains. In addition, dlkb1 mutations affect asymmetric division of larval neuroblasts (NBs); they suppress unequal cytokinesis, abrogate proper localization of Bazooka, Par-6, DaPKC and Miranda, but affect neither Pins/Galphai localization nor spindle rotation. Most aspects of the dlkb1 phenotype are exacerbated in dlkb1 pins double mutants, which exhibit more severe defects than those observed in either single mutant. This suggests that Dlkb1 and Pins act in partially redundant pathways to control the asymmetry of NB divisions. Our results also indicate that Dlkb1 and Pins function in parallel pathways controlling the stability of spindle microtubules. The finding that Dlkb1 mediates both the geometry of stem cell division and chromosome segregation provides novel insight into the mechanisms underlying tumor formation in Peutz-Jeghers patients.

The LKB1 tumor suppressor kinase in human disease.

Inactivating germline mutations in the LKB1 gene underlie Peutz-Jeghers syndrome characterized by hamartomatous polyps and an elevated risk for cancer. Recent studies suggest the involvement of LKB1 also in more common human disorders including diabetes and in a significant fraction of lung adenocarcinomas. These observations have increased the interest towards signaling pathways of this tumor suppressor kinase. The recent breakthroughs in understanding the molecular functions of the LKB1 indicate its contribution as a regulator of cell polarity, energy metabolism and cell proliferation. Here we review how the substrates and cellular functions of LKB1 may be linked to Peutz-Jeghers syndrome and other diseases, and discuss how some of the molecular changes associated with altered LKB1 signaling might be used in therapeutic approaches.

Inherited polyposis syndromes: molecular mechanisms, clinicopathology, and genetic testing.

The inherited polyposis syndromes are a group of conditions in which multiple gastrointestinal polyps occur in the lumen of the gastrointestinal tract, most exhibit an increased risk of colon cancer. Benign and malignant extraintestinal tumors might also be observed. Recent elucidation of the underlying gene mutations has contributed to our understanding of the cell biology and molecular mechanisms associated with gastrointestinal tumorigenesis. Developments have also allowed genetic testing to become an integral component in accurate diagnosis, categorization, and management of inherited polyposis syndromes. In this review, we will focus on familial adenomatous polyposis, mutY human homologue-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis, and Cowden syndrome. It is essential that both physician and patient understand the benefits and limitations of genetic testing before submission of samples to the laboratory. There are many issues accompanying molecular diagnosis of cancer syndromes, and genetic counseling is an essential prelude to genetic testing.

Tuberous sclerosis and insulin resistance. Unlikely bedfellows reveal a TORrid affair.

The TSC1-TSC2 tumor suppressor complex serves as an interface between insulin and nutrient signaling pathways and the cell growth machinery. Recent work has indicated that the TSC1-TSC2 complex plays a role in the pathobiology of a number of tumor predisposition syndromes, including tuberous sclerosis (TSC1/2), Peutz-Jeghers syndrome (LKB1), and Cowden's syndrome (PTEN), in which the TSC/Rheb/mTOR axis is inappropriately active secondary to loss of tumor suppressor function. Recent work has demonstrated that TSC deficiency imposes a negative autoregulatory loop that suppresses insulin signaling at the post-receptor level, effectively resulting in cell autonomous insulin resistance. Exploitation of this insulin signaling deficiency may hold promise among tailored clinical therapies designed to manage tuberous sclerosis.

LKB1 kinase: master and commander of metabolism and polarity.

LKB1, the product of a tumour suppressor gene, is a serine/threonine kinase that coordinates disparate cellular processes. Recent data have revealed novel functions for LKB1, providing new insight into the regulation of cell polarity and energy-generating metabolism.