OBJECTIVE: To screen for pathogenic variants in the coding regions of STK11 gene among Chinese patients with Peutz-Jeghers syndrome (PJS). METHODS: Peripheral blood samples were collected from 64 patients. The coding regions of the STK11 gene were detected by PCR and Sanger sequencing. RESULTS: Fourty-eight patients were found to harbor STK11 gene variants, which included 39 types of variants consisting of missense, nonsense, insertional, deletional and splice site variants. Among 64 PJS patients, the detection rate of point variants was 75.00% (48/64), of which missense variants accounted for 29.17% (14/48), nonsense variants accounted for 29.17%(14/48), insertion variants accounted for 2.08% (1/48), deletional variants accounted for 10.42% (5/48), and splice site variants accounted for 29.17% (14/48). The detection rates of sporadic cases and those with a family history were 71.8% (28/39) and 80.0% (20/25), respectively. Two variants (c.250A>T, c.580G>A) occurred in 3 PJS probands. Thirteen variants were unreported previously and were considered to be pathogenic. CONCLUSION The detection rate of variants among Chinese PJS patients is similar to that of other countries. A number of novel common variant sites were discovered, which enriched the spectrum of PJS-related variants.
Asian Continental Ancestry Group ; China ; DNA Mutational Analysis ; Humans ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics

Adenocarcinoma of the cervix is less common than squamous cell carcinoma. Minimal deviation adenocarcinoma (adenoma malignum) is considered an extremely well-differentiated variant of GAS. An association exists between GAS and Peutz-Jeghers syndrome, which is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple hamartomatous polyps in the gastrointestinal tracts. The incidence of GAS in patients with Peutz-Jeghers syndrome is estimated to be 11–17%. We present a rare case of adenoma malignum, diagnosed using colposcopic biopsy in a woman with Peutz-Jeghers syndrome, which was histopathologically confirmed to be GAS after surgery.
Adenocarcinoma ; Adenocarcinoma, Mucinous ; Adenoma ; Biopsy ; Carcinoma, Squamous Cell ; Cervix Uteri ; Female ; Gastrointestinal Tract ; Humans ; Incidence ; Mucins ; Peutz-Jeghers Syndrome ; Pigmentation ; Polyps ; Uterine Cervical Neoplasms

To explore the clinical features, pathological features, gene test results, diagnosis, treatment and prognosis of Peutz-Jeghers syndrome(PJS).
 Methods: We retrospectively analyzed clinical data of 46 hospitalized cases of PJS during 2007 and 2017.
 Results: All 46 patients had mucocutaneous melanin pigmentation and multiple gastrointestinal polyposis. The pigmentation was first noticed often within 5 years old, and 14 cases had family history. The clinical manifestations mainly included black spots, abdominal pain, hematochezia, and anemia. Histological examinations showed that 20 patients were classified as hamartomatous polyps,18 as adenomatous polyps, 14 as inflammatory polyps, and 10 as zigzag polyps. Eleven patients sequenced a panel of 20 genes previously associated with colorectal cancer (CRC) by next-generation sequencing, and the results showed 5 patients with gene mutations, and 3 of them with intussusception and surgical histories were found to have pathogenic germline mutations in the STK11 gene. Endoscopic treatment was the main therapy, but endoscopy combined with laparoscopy or surgical treatment was performed when complications occurred or the polyp was too large. Malignant tumors were found in 3 patients during follow-up.
 Conclusion: PJS is a hereditary disease which is characterized by spots of the skin or mucosa and gastrointestinal multiple polyps. The main pathological features are hamartoma and adenoma. The risks for intussusception and surgical operation are found to be high in the patients with pathogenic germline mutations in the STK11 gene. Endoscopic treatment is the main therapy. PJS patients should be followed up regularly due to the increasing risk for cancer and being easily to relapse.
Child, Preschool ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Neoplasm Recurrence, Local ; diagnosis ; pathology ; surgery ; therapy ; Peutz-Jeghers Syndrome ; diagnosis ; surgery ; therapy ; Protein-Serine-Threonine Kinases ; genetics ; Retrospective Studies

OBJECTIVE: The aim of this study was to evaluate the clinicopathological features of minimal deviation adenocarcinoma (MDA) and to analyze its prognostic factors. METHODS: We retrospectively analyzed the medical records of 17 patients who were diagnosed with MDA at a single institution between January 2005 and December 2015. RESULTS: The median age of the patients was 47.7 years (33–75 years). MDA was diagnosed in 7 patients (41.2%) before performing definitive surgery. Stage IB disease was diagnosed in 12 patients (70.6%) and advanced stage disease (stage II: 3, stage III: 2) in 5. MDA was incidentally diagnosed following hysterectomy for benign conditions in 6 patients. Adjuvant therapy was administered to 13 patients (76.5%). During median follow-up over 33.6 months (7–99 months), 11 patients (64.7%) showed no evidence of disease, 6 (35.3%) showed persistent or recurrent disease and 5 died of the disease. Peutz-Jeghers syndrome was not suspected in any patient, and no mutation was detected in the 3 patients who underwent genetic testing. Univariate analysis showed that advanced stage disease (P=0.016) and lymphovascular space invasion (P=0.002) demonstrated a statistically significant association with poor overall survival (OS) rates. Advanced stage disease continued to show a significant association with poor OS rates (hazard ratio, 2.92; 95% confidence interval, 1.097–7.746; P=0.032) even after multivariate analysis. CONCLUSION: Early diagnosis is important to manage MDA. Clinicians should consider MDA among the differential diagnoses in patients with a suspicious clinical presentation even with negative cervical screening tests.
Adenocarcinoma* ; Cervix Uteri* ; Diagnosis, Differential ; Early Diagnosis ; Female ; Follow-Up Studies ; Genetic Testing ; Humans ; Hysterectomy ; Mass Screening ; Medical Records ; Multivariate Analysis ; Peutz-Jeghers Syndrome ; Retrospective Studies ; Uterine Cervical Neoplasms

Although small bowel the mainly occupies the most part of the gastrointestinal tract, small intestine tumors are rare, insidious in clinical presentation, and frequently represent a diagnostic and management challenge. Small bowel tumors are generally classified as epithelial, mesenchymal, lymphoproliferative, or metastatic. Familial adenomatous polyposis and Peutz-Jeghers syndrome are the most common inherited intestinal polyposis syndromes. Until the advent of capsule endoscopy (CE) and device-assisted enteroscopy (DAE) coupled with the advances in radiology, physicians had limited diagnostic examination for small bowel examination. CE and new radiologic imaging techniques have made it easier to detect small bowel tumors. DAE allows more diagnosis and deeper reach in small intestine. CT enteroclysis/CT enterography (CTE) provides information about adjacent organs as well as pictures of the intestinal lumen side. Compared to CTE, Magnetic resonance enteroclysis/enterography provides the advantage of soft tissue contrast and multiplane imaging without radiation exposure. Treatment and prognosis are tailored to each histological subtype of tumors.
Adenomatous Polyposis Coli ; Capsule Endoscopy ; Diagnosis ; Gastrointestinal Tract ; Intestinal Polyposis ; Intestine, Small ; Peutz-Jeghers Syndrome ; Prognosis ; Radiation Exposure

Pancreatic cancer (PC) is the third most common cause of cancer-related death in the United States and the 12th most common worldwide. Mortality is high, largely due to late stage of presentation and suboptimal treatment regimens. Approximately 10% of PC cases have a familial basis. The major genetic defect has yet to be identified but may be inherited by an autosomal dominant pattern with reduced penetrance. Several known hereditary syndromes or genes are associated with an increased risk of developing PC and account for approximately 2% of PCs. These syndromes include the hereditary breast-ovarian cancer syndrome, Peutz-Jeghers syndrome, familial atypical multiple mole melanoma, Lynch syndrome, familial polyposis, ataxia-telangiectasia, and hereditary pancreatitis. Appropriate screening using methods such as biomarkers or imaging, with endoscopic ultrasound and magnetic resonance imaging, may assist in the early detection of neoplastic lesions in the high-risk population. If these lesions are detected and treated before the development of invasive carcinoma, PC disease morbidity and mortality may be improved. This review will focus on familial PC and other hereditary syndromes implicated in the increased risk of PC; it will also highlight current screening methods and the future of new screening modalities.
Ataxia Telangiectasia ; Biomarkers ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Dysplastic Nevus Syndrome ; Magnetic Resonance Imaging ; Mass Screening* ; Mortality ; Pancreatic Neoplasms* ; Pancreatitis ; Penetrance ; Peutz-Jeghers Syndrome ; Ultrasonography ; United States

No abstract available.
Peutz-Jeghers Syndrome*

Video capsule endoscopy (VCE) has expanded the range of endoscopic examination of the small bowel. The clinical application of VCE is mainly for obscure gastrointestinal bleeding (OGIB) and small bowel tumor is one of the clinically significant diagnoses of VCE, often requiring subsequent invasive interventions. Small bowel tumors are detected with a frequency of around 4% with VCE in indications of OGIB, iron deficiency anemia, unexplained abdominal pain, and others. Protruding mass with bleeding, mucosal disruption, irregular surface, discolored area, and white villi are suggested as the VCE findings of small bowel tumor. Device assisted enteroscopy (DAE), computed tomography enteroclysis/enterography and magnetic resonance enteroclysis/enterography also have clinical value in small bowel examination and tumor detection, and they can be used with VCE, sequentially or complementarily. Familial adenomatous polyposis, Peutz-Jeghers syndrome, melanoma, lymphoma, and neuroendocrine tumor with hepatic metastasis are the high risk groups for small bowel tumors, and surveillance programs for small bowel tumors are needed. VCE and radiological imaging have value in screening, and in selected cases, DAE can provide more accurate diagnosis and endoscopic treatment. This review describes the usefulness and clinical impact of VCE on small bowel tumors.
Abdominal Pain ; Adenomatous Polyposis Coli ; Anemia, Iron-Deficiency ; Capsule Endoscopy* ; Diagnosis ; Hemorrhage ; Lymphoma ; Mass Screening ; Melanoma ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Peutz-Jeghers Syndrome

Adolescent ; Fatal Outcome ; Female ; Humans ; Intussusception ; diagnosis ; etiology ; surgery ; Peutz-Jeghers Syndrome ; complications ; pathology ; surgery ; Tomography, X-Ray Computed

OBJECTIVETo correlate the clinical characteristics with mutations of the STK11 and FHIT genes in 16 patients with Peutz-Jeghers syndrome (PJS).

METHODSPotential mutations in the coding regions and flanking sequences of the STK11 and FHIT genes were detected with PCR and Sanger sequencing.

RESULTSOf the 16 patients with PJS, 8 had novel mutations in the coding region of the STK11 gene, 1 had a previously reported mutation. 1 carried a mutation in the exon 10 of the FHIT gene, which is a non-coding region. None of the mutations was detected in the immediate family members. None of the patients with STK11 gene mutations had mutation in the FHIT gene. The mutation rate of the STK11 gene among patients with PJS was 56.25%.

CONCLUSIONMutations of the STK11 gene are the major cause of PJS. Few such patients had mutations of the FHIT gene. Mutations of the FHIT gene may play a part in the pathogenesis of PJS.

Acid Anhydride Hydrolases ; genetics ; Adolescent ; Adult ; Base Sequence ; Child ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Neoplasm Proteins ; genetics ; Pedigree ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Young Adult