Solitary Peutz-Jeghers-type appendiceal hamartomatous polyp growing into the terminal ileum

Solitary Peutz-Jeghers type hamartomatous polyp is rare.It is considered to be related to a variant PeutzJeghers syndrome(PJS)and may be a separate disease entity.A 50-year-old man was referred to our hospital with a diagnosis of intussusception in the terminal ileum and underwent segmental ileal resection with appendectomy.We identified a 3.5-cm diameter polyp arising from the appendix with ingrowth into the terminal ileum.The polyp was confirmed to be a hamartomatous polyp of Peutz-Jeghers-type,histologically.However,the patient had no characteristic manifestations of PJS such as mucocutaneous pigmentation and family history.There are few reports of appendiceal hamartomatous polyp in PJS patients and solitary appendiceal hamartomatous polyp is even rarer.Also,rather than telescoping,ours is the first reported intussuscepted lesion,to the best of our knowledge.     

Duodenal cancer in a young patient with Peuts-Jeghers syndrome harboring an entire deletion of the STK11 gene

A 21-year-old woman with Peuts-Jeghers syndrome (PJS) was referred to our hospital for gastrointestinal surveillance. She had been diagnosed as having PJS from a young age based on her family history and the presence of mucocutaneous pigmentation on her lips and oral mucosa. Her mother and brother had PJS harboring an entire deletion of the STK11 gene. She had tetralogy of Fallot, atrial tachycardia, sick sinus syndrome, and mental retardation in her past history. Esophagogastroduodenoscopy identified a protruded lesion with a depressed area that occupied the lumen half-circumferentially in the duodenal second portion and also showed a 10-mm protruded lesion on the anterior wall of the lower gastric body. Colonoscopy revealed a 3-mm protruded lesion on the rectum. No polyp was found in a barium small bowel series. Biopsies were taken from the duodenal tumor and gastric and colon polyps. Histopathologically, the duodenal tumor revealed a well-differentiated tubular adenocarcinoma, whereas gastric and colon polyps showed hamartomatous polyp. Therefore, subtotal stomach-preserving pancreatoduodenectomy was performed, and subsequent histopathological examination revealed that the duodenal tumor consisted of hamartomatous polyp and a well-differentiated tubular adenocarcinoma with invasion to the muscularis propria. Immunohistochemistry revealed accumulation of nuclear p53 protein, but no accumulation of nuclear β-catenin protein. No RAS mutation was detected. Furthermore, direct sequencing of the STK11 gene in genomic DNA from peripheral blood mononuclear cells did not detect any mutation initially. However, multiplex ligation-dependent probe amplification (MLPA) analysis revealed entire deletion of STK11. These findings suggest that entire deletion of the STK11 gene caused hamartomatous polyps in the entire gastrointestinal tract and, subsequently, duodenal polyps likely gave rise to cancer through p53 mutation.     

Appendiceal carcinoid in a pediatric patient with Peutz-Jeghers syndrome: A case report and comprehensive literature review

Rationale:Peutz-Jeghers syndrome (PJS), a rare autosomal dominant disorder, is characterized by mucocutaneous pigmentations, hamartomatous polyps in the gastrointestinal tract, and a high risk of developing various malignancies. To the best of our knowledge, only 1 case of appendiceal carcinoid associated with PJS has been previously reported in the pediatric population.Patient concerns:We report a 7-year-old girl who was admitted for severe, intermittent abdominal pain and cramps, nausea, and vomiting. Multiple brown melanotic macules on the lips, buccal mucosa, and the tongue were noted.Diagnosis:A plain abdominal X-ray in a standing position revealed dilated intestinal loops with multiple air-fluid levels. A computed tomography scan of the abdomen showing a “coffee bean” appearance of the jejunal loop with a transition point to the duodenal loop. Axial-contrast-enhanced computed tomography scan of the abdomen showing dilated jejunum loops, filled with fluid with the swirled appearance of mesentery typical for volvulus. The diagnosis of PJS was based on clinical findings along with the histopathologic confirmation of the hamartomatous polyps.Interventions:An emergency laparotomy was performed, revealing a jejunojejunal intussusception starting 40 cm from the duodenojejunal flexure. Jejunotomy revealed that a lead-point intussusception was a necrotic hamartomatous polyp. After resecting the involved jejunal necrotic segment, including the polyp, end-to-end jejuno-jejunal anastomosis was performed. Further exploration revealed the presence of a jejunal mass 80 cm from the duodenojejunal flexure identified as another hamartomatous pedunculated polyp. The polyp was resected, and the enterotomy was then closed transversely. The grossly normal appendix was also removed.Outcomes:Clinical findings along with the histopathologically confirmed hamartomatous polyps were consistent with PJS. An appendiceal carcinoid (well-differentiated neuroendocrine tumor, European Neuroendocrine Tumor Society stage pT2) was incidentally detected during histological examination of the appendix. The patient and parents were counseled accordingly, focusing on active surveillance and control of symptoms. Two additional hamartomatous polyps (gastric and jejunal) were detected endoscopically and resected in the fourth postoperative week. A regular, 1-year follow-up and surveillance revealed no complications or recurrences.Lessons:Unusual neoplasms can occasionally be encountered in well-defined syndromes such as PJS. Therefore, active follow-up and surveillance are mandatory for all patients with PJS.     

STK11/LKB1 germline mutations in the first Peutz-Jeghers syndrome patients identified in Slovakia

Peutz-Jeghers syndrome (PJS) is characterized by number of hamartomatous polyps in the gastrointestinal tract and by mucocutaneous hypermelanocytic lesions at different sites. Older patients have an increased risk of the cancers of small intestine, stomach, pancreas, colon, esophagus, ovary, testis, uterus, breast and lung. In majority of PJS cases, the germline mutations in serine/threonine kinase STK11/LKB1 gene were found to be associated with disease. Here we report the results of a first mutational screen of STK11/LKB1 in PJS patients characterized in Slovak population. The first patient with unusual carcinoma of duodenum was a sporadic case and carried c.842delC change residing in a mutational C6 repeat hotspot. Neither the polyp nor the tumor of the patient displayed the loss of heterozygosity at the site of mutation suggesting different mechanism involved in the formation of polyp and tumor in this case. The second patient belonged to a three-generation family with typical PJS features but not cancers. Interestingly, the patient displayed concomitant occurrence of adenomatous and hamartomatous polyps. Molecular analysis revealed an IVS2+1A>G mutation that alters the second intron 5' splice site and was shown to lead to aberrant splicing mediated by the U12-dependent spliceosome. The same mutation was present in the 9 affected members of the family but in none of their normal relatives. We also observed novel c. IVS2+61G>A unclassified variant, and recurrent IVS2+24G>T and 3UTR+129C>T polymorphisms. Based on the achieved results, we could offer predictive genetic testing and counseling to other members of the patient's families.     

Course and follow-up of solitary Peutz-Jeghers polyps: a case series

BACKGROUND AND AIMS: Peutz-Jeghers syndrome (PJS) is a rare, autosomal-dominant disease characterized by hamartomatous polyps of the alimentary tract, hyperpigmentation of the skin, and family history of PJS. Rarely, solitary Peutz-Jeghers polyps (PJP) arise in patients without other features of PJS. PATIENTS AND METHODS: We reviewed eight patients since 1979 with solitary PJP, six men and two women. RESULTS: The average age at diagnosis was higher (56+/-13 years) than that of PJS patients in the literature. Polyps were found in the sigmoid colon ( n=4), cecum ( n=1), stomach ( n=1), and duodenum ( n=2). The colonic polyps were diagnosed and removed endoscopically. Indications for colonoscopy included routine screening ( n=4) or rectal bleeding ( n=1). The duodenal and gastric polyps were diagnosed and removed during gastroduodenoscopic examinations, which were performed for nonspecific dyspepsia ( n=2) or gastrointestinal bleeding ( n=1). The median size was 20 mm (range 2 mm-25 mm). Patients were followed for a median of 11.5 years (range 3-22) without another PJP or cancer. Three patients died of causes unrelated to PJP. Five patients are alive and polyp free. CONCLUSION: Solitary PJP do not carry a risk of gastrointestinal cancer and are not an indication for specific high-risk screening.     

Three cases of Solitary Peutz-Jeghers-type hamartomatous polyp in the duodenum

A solitary Peutz-Jeghers-type hamartomatous polyp in the duodenum is rare, and few reports have described its characteristic endoscopic features. We describe three cases of solitary Peutz-Jeghers-type hamartomatous polyp and their endoscopic findings in detail. The polyp in all of our three cases showed an irregularly lobular or nodular surface, whereas adenomas often show a regularly nodular or granular surface. The color of the polyp was whitish in all of our cases. In the present cases, close observation by endoscopy revealed that the solitary Peutz-Jeghers-type hamartomatous polyps looked whitish because of the presence of diffusely scattered white spots on the surface of the polyps. Duodenal polyps that exhibit the aforementioned endoscopic characteristics may be diagnosed as Peutz-Jeghers-type hamartomatous polyps and treated by polypectomy because of the malignant potential.     

An Incidentally Discovered Asymptomatic Para-Aortic Paraganglioma with Peutz-Jeghers Syndrome

Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder characterized by mucocutaneous melanin pigmentation and gastrointestinal (GI) tract hamartomatous polyps and an increased risk of malignancy. In addition to polyposis, previous studies have reported increased risk of GI and extraGI malignancies in PJS patients, compared with that of the general population. The most common extraintestinal malignancies reported in previous studies are pancreatic, breast, ovarian and testicular cancers.We report the case of a 17-year-old boy who presented with generalized weakness, recurrent sharp abdominal pain and melena, had exploratory laparotomy and ileal resection for ileo-ileal intussusception. Pigmentation of the buccal mucosa was noted. An abdominal computed tomography scan (CT) revealed multiple polyps in small bowel loops. Gastroscopy revealed multiple dimunitive polyps in stomach and pedunculated polyp in duodenum. Colonoscopy revealed multiple colonic polyps. Pathological examination of the polyps confirmed hamartomas with smooth muscle arborization, compatible with Peutz-Jeghers polyps. CT scan guided left para-aortic lymph node biopsy revealed the characteristic features of extra-adrenal para-aortic paraganglioma. Although cases of various GI and extra GI malignancies in PJS patients has been reported, the present case appears to be the first in literature in which the PJS syndrome was associated with asymptomatic extraadrenal para-aortic paraganglioma. Patients with PJS should be treated by endoscopic or surgical resection and need whole-body screening.     

Duodenal and ampullary obstruction by a Peutz-Jeghers polyp

We report a case of Peutz-Jeghers syndrome presenting with obstruction of the second part of the duodenum and the ampulla of Vater by a large intra-luminal polyp leading to duodenal obstruction and obstructive jaundice. CT scan of the abdomen showed a large polypoidal lesion, a caecal polyp and jejuno-jejunal intussusception. At surgery, two intussusceptions were reduced and leading polyps were excised via two enterotomies; the caecal polyp was excised via caecotomy. The duodenal polyp was excised by limited duodenectomy after frozen section has shown no evidence of malignancy. Histopathological study of all the excised polyps including that of the duodenum showed hamartomatous polyps with no malignant changes. Apart from acute bleeding, this case highlights many of the surgical gastrointestinal complications of Peutz-Jeghers syndrome. It also highlights the unusual combined duodenal and common bile duct obstruction by a large Peutz-Jeghers polyp. The controversial association of this syndrome with cancer and management options is also discussed.     

A Small Polyp of Brunner's Gland Hyperplasia Causing Hemorrhage

Abstract: A rare case of a small Brunner's gland hyperplasia (BGH) of the duodenum which represented hemorrhage is presented. An 84-year-old male was admitted because of tarry stool and anemia. Endoscopic examination revealed a small, subpedunculated duodenal polyp with blood and clots on its surface, which was considered responsible for the tarry stool. The lesion was polypectomized without any complications. Since complications of BGH including bleeding and obstruction, are more likely to occur as the size of the lesion increases, small BGH lesions tend to be regarded as benign and are left alone in clinical settings. The present case showed the possibility that such a seemingly harmless small polyp may eventually lead to massive hemorrhage. (Dig Endosc 1999; 11: 52–54)     

Solitary Hamartomatous Polyp of the Duodenum in the Absence of Familial Polyposis

A large hamartomatous polyp of the Peutz-Jegher type was discovered in the distal duodenum by endoscopy in a patient with occult gastrointestinal bleeding. There were no other polyps in the gastrointestinal tract and the patient lacked any stigmata associated with the familial polyposis syndromes. This is the second well-documented case of an isolated hamartomatous polyp of the Peutz-Jegher type in the small intestine occurring in the absence of familial polyposis.     

Novel serine/threonine kinase 11 gene mutations in Peutz-Jeghers syndrome patients and endoscopic management

AIM: To explore mutations in serine/threonine kinase 11 (STK11) gene in Peutz-Jeghers syndrome (PJS) with gastrointestinal (GI) hamartomatous polyps.METHODS: Six Japanese PJS patients in 3 families were enrolled in this study. Each of the cases had hamartomatous polyposis in the gastrointestinal tract, including the small intestine, along with mucocutaneous hyperpigmentation. Narrow-band imaging (NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions. NBI magnification findings could be classified into three groups (type A, type B, or type C). Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy. Genomic DNA was extracted from a whole blood sample from each subject. All of the coding exons of STK11 gene, its boundary regions, and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction, and direct sequencing was performed to assess the germline mutations.RESULTS: NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps. Overall, we found 5 cases of type A and one case without the examination for the gastric polyps, while there were 4 cases of type B and 2 case of type A for the colorectal polyps. Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications. The only delayed complication included the occurrence of bleeding in a case, and this was successfully managed with hemoclips. Resected polyps contained no malignant components. Based on mutation analysis, all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5, which resulted in the production of a truncated protein (Q220X). In Family II, a case had -252C>A and -193C>A in the promoter region. In Family III, a case was found to have the +1062C>G (F342L) mutation in exon 8.CONCLUSION: We found two novel mutations of STK11 in association with PJS. Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.     

Mutation analysis of related genes in hamartoma polyp tissue of Peutz-Jeghers syndrome

BACKGROUND Peutz-Jeghers syndrome(PJS) is a rare disease with clinical manifestations of pigmented spots on the lips, mucous membranes and extremities, scattered gastrointestinal polyps, and susceptibility to tumors. The clinical heterogeneity of PJS is obvious, and the relationship between clinical phenotype and genotype is still unclear.AIM To investigate the mutation status of hereditary colorectal tumor-associated genes in hamartoma polyp tissue of PJS patients and discuss its relationship with the clinicopathological data of PJS.METHODS Twenty patients with PJS were randomly selected for this study and were treated in the Air Force Medical Center(former Air Force General Hospital) PLA between 2008 and 2017. Their hamartoma polyp tissues were used for APC,AXIN2, BMPR1A, EPCAM, MLH1, MLH3, MSH2, MSH6, MUTYH, PMS1, PMS2,PTEN, SMAD4, and LKB1/STK11 gene sequencing using next-generation sequencing technology. The correlations between the sequencing results and clinical pathological data of PJS were analyzed.RESULTS Fourteen types of LKB1/STK11 mutations were detected in 16 cases(80.0%), of which 8 new mutations were found(3 types of frameshift deletion mutations:c.243 del G, c.363_364 del GA, and c.722 del C; 2 types of frameshift insertions: c.144_145 ins GCAAG, and c.454_455 ins C; 3 types of splice site mutations:c.464+1 GT, c.464+1 GA, and c.598-1 GA); 9 cases(45.0%) were found to have 18 types of heterozygous mutations in the remaining 13 genes except LKB1/STK11. Of these, MSH2: c.792+1GA, MSH6: c.3689CG,c.4001+13CCTTAC, PMS1: c.46Ct, and c.922GA were new mutations.CONCLUSION The genetic mutations in hamartoma polyp tissue of PJS are complex and diverse.Moreover, other gene mutations in PJS hamartoma polyp tissue were observed,with the exception of LKB1/STK11 gene, especially the DNA mismatch repair gene(MMR). Colorectal hamartoma polyps with LKB1/STK11 mutations were larger in diameter than those with other gene mutations.     

Extraintestinal polyps in Peutz-Jeghers syndrome: presentation of four cases and review of the literature

Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder characterized by hamartomatous polyps in the gastrointestinal tract and typical pigment lesions. Extraintestinal polyps have rarely been reported. Possible sites include the respiratory tract, urogenital tract, and gallbladder. We here describe four cases of extraintestinal polyps in PJS patients and review the literature on the need for operative therapy of extraintestinal polyps in PJS. Three nonrelated patients were examined who had PJS and polyps in the gallbladder; the fourth patient had PJS and recurrent choanal polyps. Surgery has so far been performed only for symptomatic polyps: one laparoscopic cholecystectomy and removal of the choanal polyps for recurrent infections of the respiratory tract. The remaining two patients reported no symptoms from the extraintestinal polyps. No malignant transformation was found in these patients, nor has such been reported in the literature on PJS. The frequent observation of this manifestation in our patients raises the question of clinical management: Is prophylactic surgery indicated? Since malignant transformation of PJS polyps in the intestine is extremely rare we see no reason for operative therapy as long as the polyps are small and asymptomatic. Regular sonographic controls are recommended since the risk of malignant transformation cannot be ruled out at present.     

Molecular insights into Peutz-Jeghers syndrome: two probands with a germline mutation of <Emphasis Type="Italic">LKB1</Emphasis>

LKB1 encodes a serine/threonine protein kinase that is defective in patients with Peutz-Jeghers syndrome (PJS), a hereditary disorder characterized by gastrointestinal hamartomatous polyposis and an increased risk of cancer development. Although a tentative molecular classification of PJS patients was recently made according to their LKB1 mutation status, it is difficult to clarify the genotype-phenotype relationship because of the rarity and genetic heterogeneity of this disease. Here we report on two probands with PJS whose intestinal hamartomatous polyposis was treated by laparoscopyassisted polypectomy. Direct sequencing analyses revealed a nonsense mutation at codon 240 in exon 5 in one patient, and a mutation at a splicing donor site in intron 5 in the other patient. No additional somatic mutations were detected in the resected hamartomas in either case. Immunohistochemical analysis revealed an elevated expression of cyclooxygenase-2, and almost complete loss of LKB1 expression in the polyps, suggesting that a biallelic inactivation of the LKB1 gene was responsible for the hamartoma formation. Methylation-specific polymerase chain reaction analysis revealed no hypermethylation of the LKB1 promoter. Mutation analysis is useful in making a precise diagnosis of PJS in candidate probands, and may in the near future provide valuable information for predicting cancer risk based on genotype-phenotype correlations.     

Peutz-Jeghers syndrome： Diagnostic and therapeutic approach

Peutz-Jeghers syndrome (PJS) is an inherited, autosomal dominant disorder distinguished by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous lesions.Prevalence of PJS is estimated from 1 in 8300 to 1 in 280 000 individuals.PJS predisposes sufferers to various malignancies (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular tumors).Bleeding, obstruction and intussusception are common complications in patients with PJS.Double balloon enteroscopy (DBE) allows examination and treatment of the small bowel.Polypectomy using DBE may obviate the need for repeated urgent operations and small bowel resection that leads to short bowel syndrome.Prophylaxis and polypectomy of the entire small bowel is the gold standard in PJS patients.Intraoperative enteroscopy (IOE) was the only possibility for endoscopic treatment of patients with PJS before the DBE era.Both DBE and IOE facilitate exploration and treatment of the small intestine.DBE is less invasive and more convenient for the patient.Both procedures are generally safe and useful.An overall recommendation for PJS patients includes not only gastrointestinal multiple polyp resolution, but also regular lifelong cancer screening (colonoscopy, upper endoscopy, computed tomography, magnetic resonance imaging or ultrasound of the pancreas, chest X-ray, mammography and pelvic examination with ultrasound in women, and testicular examination in men).Although the incidence of PJS is low, it is important for clinicians to recognize these disorders to prevent morbidity and mortality in these patients, and to perform presymptomatic testing in the first-degree relatives of PJS patients.     

Synchronous presentation of acute pancreatitis and splenomegaly with intussusceptions in Peutz‐Jeghers syndrome

Peutz‐Jeghers syndrome (PJS) is a rare, autosomal dominant inherited disorder characterized by gastrointestinal hamartomatous polyps and pigmented mucocutaneous lesions. Intussusceptions and gastrointestinal tract bleeding are frequent complications of PJS caused by larger polyps, but acute pancreatitis and splenomegaly are very rare. Previously, surgical intervention was the only curative modality despite the associated complications. In recent years, double‐balloon enteroscopy (DBE) has become the alternative method as the ideal treatment. We report the case of a 20‐year‐old woman diagnosed with PJS, as she suffered from 4‐day nausea and vomiting with acute abdominal pain, and clinically manifested acute pancreatitis, splenomegaly and duodenojejunal intussusceptions secondary to a huge proximal jejunal polyp (10 cm × 2 cm). We removed the polyp via DBE and found that the acute pancreatitis, splenomegaly and duodenojejunal intussusceptions were simultaneously ameliorated 2 days after treatment. Currently, the patient has been symptom free for 3 months after polypectomy. Acute pancreatitis, splenomegaly and intussusceptions can synchronously occur in PJS patients, and polypectomy via DBE is the effective treatment alternative to surgical intervention for this disease, thereby obviating some complications associated with the latter.     

Clinical features,endoscopic polypectomy and STK11 gene mutation in a nine-month-old Peutz-Jeghers syndrome Chinese infant

AIM: To investigate multiple polyps in a Chinese PeutzJeghers syndrome(PJS) infant. METHODS: A nine-month-old PJS infant was admitted to our hospital for recurrent prolapsed rectal polyps for one month. The clinical characteristics, a colonoscopic image, the pathological characteristics of the polyps and X-ray images of the intestinal perforation were obtained. Serine threonine-protein kinase 11(STK11) gene analysis was also performed using a DNA sample from this infant.RESULTS: Here we describe the youngest known Chinese infant with PJS. Five polyps, including a giant polyp of approximately 4 cm × 2 cm in size, were removed from the infant's intestine. Laparotomy was performed to repair a perforation caused by pneumoperitoneum. The pathological results showed that this child had PJS. Molecular analysis of the STK11 gene further revealed a novel frameshift mutation(c.64_65het_del AT) in exon 1 in this PJS infant.CONCLUSION: The appropriate treatment method for multiple polyps in an infant must be carefully considered. Our results also show that the STK11 gene mutation is the primary cause of PJS.     

Endoscopic snare papillectomy for a solitary Peutz-Jeghers-type polyp in the duodenum with ingrowth into the common bile duct: Case report

Solitary duodenal Peutz-Jeghers (PJ)-type hamartomatous polyps are rare and considered a different disease entity than classic PJ syndrome. We describe the case of an 89-year-old man admitted to our emergency department with symptoms of acute cholangitis, liver dysfunction, and slight jaundice. Magnetic resonance imaging showed multiple signal voids, reflecting choledocholithiasis, and an oval-shaped tumor in the common bile duct (CBD). Following endoscopic retrograde cholangiopancreatography, the patient was diagnosed with a lower CBD tumor 20 mm in diameter. Endoscopic sphincterotomy was performed for choledocholithotomy, resulting in the expulsion of a large tumor with a stalk connected to the papilla of Vater. The tumor was successfully excised en bloc by endoscopic snare papillectomy. Histopathologic examination showed that the tumor was a PJ-type hamartomatous polyp. No mucocutaneous pigmentation of the skin was evident and the patient’s family history was negative. Solitary duodenal PJ-type hamartomatous polyps are usually diagnosed incidentally during endoscopy for other indications because most of these tumors are asymptomatic or have nonspecific presentations. To our knowledge, this is the first reported solitary PJ-type polyp with intra-CBD growth treated by endoscopic snare papillectomy.     

Peutz-Jeghers' syndrome with malignant development in a hamartomatous polyp: report of one case and review of the literature

The malignant potential of hamartomatous polyps in Peutz-Jeghers' (PPJ) syndrome has been debated. Although it is a very rare event, these polyps can become malignant, as demonstrated by this report. One case of colonic adenocarcinoma associated with Peutz-Jeghers' syndrome is described in a 62-year-old woman. The patient had colonic carcinoma which developed in a hamartomatous polyp. The malignant development of this colonic hamartomatous polyp arising in Peutz-Jeghers' syndrome was pathologically confirmed at surgery. This case also shows a sequence of hamartoma-dysplasia-carcinoma in a hamartomatous polyp without adenomatous changes. This suggests that hamartomatous polyps in Peutz-Jeghers' syndrome may develop into adenocarcinoma and may be a precursor of gastrointestinal carcinomas. STK 11 is a tumor suppressor gene regulating the development of hamartomas, and this somatic mutation promotes gastrointestinal cancer at later stages in Peutz-Jeghers' syndrome.