Unusual case of small bowel intussusception in adult revealing a Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is a rare genetic disorder characterized by hyperpigmented mucocutaneous macules, hamartomatous polyps of the small intestine, and family history. These hamartomatous polyps can cause intermittent abdominal pain, chronic anemia, or even intussusception. Imaging has an important role in the diagnosis of this syndrome but also in the identification of complications and periodic surveillance. Here we present a demonstrative case of a Peutz-Jeghers syndrome associated with intussusception in a 16-year-old patient.

Peutz–Jeghers Syndrome and the Role of Imaging: Pathophysiology, Diagnosis, and Associated Cancers

The Peutz-Jeghers Syndrome (PJS) is an autosomal dominant neoplastic syndrome defined by hamartomatous polyps through the gastrointestinal tract, development of characteristic mucocutaneous pigmentations, and an elevated lifetime cancer risk. The majority of cases are due to a mutation in the STK11 gene located at 19p13.3. The estimated incidence of PJS ranges from 1:50,000 to 1:200,000. PJS carries an elevated risk of malignancies including gastrointestinal, breast, lung, and genitourinary (GU) neoplasms. Patients with PJS are at a 15- to 18-fold increased malignancy risk relative to the general population. Radiologists have an integral role in the diagnosis of these patients. Various imaging modalities are used to screen for malignancies and complications associated with PJS. Awareness of various PJS imaging patterns, associated malignancies, and their complications is crucial for accurate imaging interpretation and patient management. In this manuscript, we provide a comprehensive overview of PJS, associated malignancies, and surveillance protocols.

Epithelial gastric polyps

Gastric polyps are lesions projected above the mucosal surface, which are detected in approximately 1–6% of upper gastrointestinal endoscopies. Based to their shape, polyps are classified as pedunculate, semi-pedunculate, sessile and flat. Depending on the histopathological type, some of them have the potential to transform into adenocarcinoma. Polyps can be of epithelial and non-epithelial origin. The first group, which is discussed in greater detail in this paper, includes fundic gland polyps, hyperplastic, adenomatous and hamartomatous polyps. Non-epithelial polyps include stromal tumours, leiomyomas, fibrous inflammatory polyps, fibroids, fibromyomas, lipomas, ectopic pancreas, neuroendocrine tumours, neuromas, and some vascular lesions. Multiple polyps in patients under the age of 40 years require more extensive diagnosis for hereditary polyposis syndromes, which are associated with an increased risk of gastric cancer, as well as other gastrointestinal and extra-gastrointestinal malignancies. In recent years, there has been a clear decrease in the proportion of hyperplastic polyps and an increase in the proportion of fundic gland polyps among all gastric polyps, which is probably related to the increased use of proton pump inhibitors and a reduced incidence of Helicobacter pylori infections. About 90% of gastric polyps are detected accidentally and usually do not cause clinical symptoms, but large polyps may be responsible for anaemia, bloody stools, abdominal pain, and even pyloric obstruction, which may be manifested by vomiting, severe flatulence, lack of appetite or progressive weight loss.

Gene of the month: STK11

STK11 encodes for the protein liver kinase B1, a serine/threonine kinase which is involved in a number of physiological processes including regulation of cellular metabolism, cell polarity and the DNA damage response. It acts as a tumour suppressor via multiple mechanisms, most classically through AMP-activated protein kinase-mediated inhibition of the mammalian target of rapamycin signalling pathway. Germline loss-of-function mutations in STK11 give rise to Peutz-Jeghers syndrome, which is associated with hamartomatous polyps of the gastrointestinal tract, mucocutaneous pigmentation and a substantially increased lifetime risk of many cancers. In the sporadic setting, STK11 mutations are commonly seen in a subset of adenocarcinomas of the lung in addition to a number of other tumours occurring at various sites. Mutations in STK11 have been associated with worse prognoses across a range of malignancies and may be a predictor of poor response to immunotherapy in a subset of lung cancers, though further studies are needed before the presence of STK11 mutations can be implemented as a routine clinical biomarker.

Peutz-Jeghers syndrome: what has been known for 125 years of research? (review)

Peutz-Jeghers syndrome (PJS) is an extremely rare autosomal dominant hereditary disease characterized by the growth of hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmented macules and an increased risk of malignant neoplasms of various localizations. In most cases the development of PJS is associated with the presence of a mutation in the STK11 gene, but not all patients have this mutation. This review presents the historical aspects of the first data on PJS, considers the clinical manifestations of the disease, current diagnostic methods, as well as recent knowledge about the genetic causes, about the risk of malignant neoplasms in patients with PJS, existing guidelines for screening and treatment of patients with PJS. However, the presence of a number of unresolved issues in genetics, monitoring and treatment indicates the need for further research.

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

Background Peutz-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 presentation A 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. Conclusions Transurethral 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.

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

Background Peutz–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 presentation A 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. Conclusions Laparoscopic-assisted disinvagination and polypectomy is a useful, minimally invasive treatment for multiple intussusceptions caused by small intestinal polyps in patients with PJS.

Germline testing of patients with personal history of colorectal polyposis by cancer genetics counseling services.

47 Background: National Comprehensive Cancer Network (NCCN) guidelines recommend that individuals with >10 adenomatous polyps, ≥2 hamartomatous polyps, or ≥5 serrated polyps proximal to the sigmoid colon have detailed risk assessment and potential genetic testing to rule out polyposis syndrome. Here, we describe germline testing of patients with a personal history of colorectal polyposis by Cancer Genetics Counseling Services. Methods: This is an IRB-approved retrospective chart-review study. Between 2016 and 2020, 1011 unique genetic counseling visits were conducted. Germline testing was recommended by a certified genetic counselor if medically necessary. All patients with a personal history of colorectal polyposis were identified (N=20) and their germline testing results were summarized. Results: The reasons for referral to the Cancer Genetics Counseling Services were personal history of >10 adenomatous polyps (N=13), personal and family history of colorectal polyposis (N=3), personal history of juvenile colorectal polyps (N=3) or personal history of ≥2 hamartomatous polyps (N=1). The median age is 58 years-old (1-84). Ten (50%) patients were females. Caucasians, African Americans and other ethnic backgrounds represented 80%, 10% and 10% respectively. In our cohort, 6 out of 20 (30%) patients had a pathogenic germline mutation, 5 (25%) patients had variant of unknown significance (VUS) and 9 (45%) patients had negative testing. Among patients with pathogenic germline mutations, 3 patients had a pathogenic APC mutation (APC c.1659G>A, APC c.2802C>A and APC c.1643dupT) and were diagnosed with Familial Adenomatous Polyposis (FAP). One patient had 2 pathogenic MUTYH mutations (MUTYH c.536A>G and MUTYH c.1187G>A) and was diagnosed with One patient had a pathogenic PTEN c.634+5G>A mutation and was diagnosed with PTEN Hamartoma Tumor Syndrome. Among the 3 patients with a personal history of juvenile colorectal polyps, one patient had a CHEK2 c.190G>A mutation while the other two had negative genetic test results. The VUS mutations in our cohort were MRE11A c.826C>T, BLM c.3478T>C, BRCA2 c.2519T>C, CHEK2 p.V395L and CTNNA1 c.392dupT. Conclusions: In our cohort of patients with personal history of colorectal polyposis, the majority of patients (45%) had negative germline testing. An underlying pathogenic germline mutation and VUS were identified in 30% and 25% of the patients, respectively. FAP Syndrome was the most commonly diagnosed hereditary polyposis syndrome with 3 patients found to have APC germline mutations. Other pathogenic mutations were identified in the MUTYH, PTEN and CHEK2 genes. Patients with MUTYH and PTEN mutations were diagnosed with MAP and PTEN Hamartoma Tumor Syndromes respectively.