Abstract
Purpose
To investigate the recent incidence of malignant tumors associated with Peutz–Jeghers syndrome (PJS) in Japan to clarify if there are any differences in malignant tumor risk and the spectrum of malignancies by reviewing the literature on this subject.
Methods
We reviewed PJS cases reported in 1115 papers in Japan between January, 1989 and December, 2014.
Results
Malignant tumors were identified in 186 of the total 583 PJS cases from 523 evaluable studies. The estimated cumulative risk of a malignant tumor was 83.0 % at 70 years of age. Compared with a previous study, on a collective 91 cases reported up until 1988 in Japan, the reported proportion of gastrointestinal malignancies decreased, from 82.4 to 48.3 %, whereas that of gynecological malignancies increased, from 8.8 to 34.3 % (P < 0.01). Moreover, breast cancers were occasionally reported (4.8 %), even though none were reported in the previous study. Adenocarcinoma of the uterine cervix was the most common malignant tumor (46.8 %) among women with PJS.
Conclusions
The increased number of reports of cervical adenocarcinoma in women with PJS is the prominent trend in Japan, and a subject of concern among gynecologists. The risk of breast cancer seems to be increasing, but confirmation of this trend will require further investigation.
Similar content being viewed by others
References
Bruwer A, Bargen JA, Kierland RR. Surface pigmentation and generalized intestinal polyposis; (Peutz–Jeghers syndrome). Proc Staff Meet Mayo Clin. 1954;29:168–71.
Hemminki A, Markie D, Tomilton I, Avizienyte E, Roth S, Loukola A, et al. A serine/threonine kinase gene defective in Peutz–Jeghers syndrome. Nature. 1998;391:184–7.
Giadiello FM, Trimbath JD. Peutz–Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol. 2006;4:408–15.
Hutchinson J. Pigmentation of lips and mouth. Arch Surg. 1896;7:290–1.
Beggs AD, Latchford AR, Vasen HFA, Moslein G, Alonso A, Arets S, et al. Peutz–Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010;59:975–86.
Latchford AR, Neale K, Philips RKS, Clark SK. Peutz–Jeghers syndrome: intriguing suggestion of gastrointestinal cancer prevention from surveillance. Dis Colon Rectum. 2011;54:1547–51.
Kapocova M, Tached I, Rejchrt S, Bures J. Peutz–Jeghers syndrome: diagnostic and therapeutic approach. World J Gastroenterol. 2009;15:5397–408.
van Lier MGF, Wagner A, Mathus-Viegen EMH, Kuipers EJ, Steyerberg EW, van Leedam ME. High cancer risk in Peutz–Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastoenterol. 2010;105:1258–64.
Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, et al. Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology. 2000;119:1447–53.
Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, et al. Frequency and spectrum of cancers in the Peutz–Jeghers syndrome. Clin Cancer Res. 2006;12:3209–15.
Iwama T, Ishida H, Imajo M, Takemura K, Aoki N, Mishima Y. The Peutz–Jeghers syndrome and malignant tumor. In: Proceedings of the fourth international symposium on colorectal cancer (ISCC-4). Joji Utsunomiya and Henry T. Lynch (Edt) Springer, Tokyo, 1990.
Aaltonen LA. Hereditary intestinal cancer. Semin Cancer Biol. 2000;10:289–98.
Aretz S, Stienen D, Uhlhaas S, Loff S, Back W, Pagenstecher C, et al. High proportion of large genomic STK11 deletions in Peutz–Jeghers syndrome. Hum Mutat. 2005;26:513–9.
Silverberg SG, Hurt WG. Minimal deviation adenocarcinoma (“adenoma malignum”) of the cervix: a reappraisal. Am J Obstet Gynecol. 1975;121:971–5.
Utsunomiya J, Gocho H, Miyanaga T, Hamaguchi E, Kashimure A. Peutz–Jeghers syndrome: its natural course and management. John Hopkins Med J. 1975;136:71–82.
Schumacher V, Vogel T, Leube B, Driemel C, Goecke T, Möslein G, et al. STK11 genotyping and cancer risk in Peutz–Jeghers syndrome. J Med Genet. 2005;42:428–35.
Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJ, Gittelsohn AM, Booker SV, et al. Increased risk of cancer in the Peutz–Jeghers syndrome. New Eng J Med. 1987;316:1511–4.
Spigelman AD, Murday V, Phillips RK. Cancer and the Peutz–Jeghers syndrome. Gut. 1989;30:1588–90.
Boadman LA, Thibodeau SN, Schaid DJ, Lindor NM, McDonnell SK, Burgart LJ, et al. Increased risk for cancer in patients with the Peutz–Jeghers syndrome. Ann Intern Med. 1998;128:896–9.
Linos DA, Dozois RR, Dahlin DC, Bartholomew LG. Does Peutz–Jeghers syndrome predispose to gastrointestinal malignancy? A later look. Arch Surg. 1981;116:1182–4.
Choi HS, Park YJ, Youk EG, Yoon KA, Ku JL, Kim NK, et al. Clinical characteristics of Peutz–Jeghers syndrome in Korean polyposis patients. Int J Colorectal Dis. 2000;15:35–8.
Hizawa K, Iida M, Matsumoto T, Kohrogi N, Kinoshita H, Yao T, et al. Cancer in Peutz–Jeghers syndrome. Cancer. 1993;72:2777–81.
Laughlin EH. Benign and malignant neoplasms in a family with Peutz–Jeghers syndrome: study of three generations. South Med J. 1991;84:1205–9.
Lim W, Olschwang S, Keller JJ, Westerman AM, Menko FH, Boardman LA, et al. Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology. 2004;126:1788–94.
Mehenni H, Resta N, Park JG, Miyaki M, Guanti G, Costanza MC. Cancer risks in LKB1 germline mutation carriers. Gut. 2006;55:984–90.
Resta N, Pierannunzio D, Lenato GM, Stella A, Capocaccia R, Bagnulo R, et al. Cancer risk associated with STK11/LKB1 germline mutations in Peutz–Jeghers syndrome patients: results of an Italian multicenter study. Dig Liver Dis. 2013;45:606–11.
Aretz S, Stienen D, Uhlhaas S, Loff S, Back W, Pagenstecher C, et al. High proportion of large genomic STK11 deletions in Peutz–Jeghers syndrome. Hum Genet. 2005;26:513–9.
Mehenni H, Gehrig C, Nezu J, Oku A, Shimane M, Rossier C, et al. Loss of LKB1 kinase activity in Peutz–Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Genet. 1998;63:1641–50.
Lim W, Olschwang S, Keller JJ, Westerman AM, Menko FH, Boardman LA, et al. Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology. 2004;126:1788–94.
Kaku T, Hachisuga T, Toyoshima S, Enjoji M, Mori T, Nagaoka M. Extremely well-differentiated adenocarcinoma (“adenoma malignum”) of the cervix in a patient with Peutz–Jeghers syndrome. Int J Gynecol Pathol. 1985;4:266–73.
Srivatsa PJ, Keeney GL, Podratz KC. Disseminated cervical adenoma malignum and bilateral ovarian sex cord tumors with annular tubules associated with Peutz–Jeghers syndrome. Gynecol Oncol. 1994;53:256–64.
Ueki A, Kisu I, Banno K, Yanokura M, Masuda K, Kobayashi Y, et al. Gynecological tumors in patients with Peutz–Jeghers syndrome (PJS). Open J Genet. 2011;1:65–9.
von Hochstetter AR, Ess D, Bannwart F, Bühler H. Adenocarcinoma of the cervix in Peutz–Jeghers syndrome. Case report and review of the literature. Schweiz Med Wochenschr. 1987;117:1910–4.
Nucci MR, Clement PB, Young RH. Lobular endocervical glandular hyperplasia, not otherwise specified: a clinicopathologic analysis of thirteen cases of a distinctive pseudoneoplastic lesion and comparison with fourteen cases of adenoma malignum. Am J Surg Pathol. 1999;23:886–91.
Hirasawa A, Akahane T, Tsuruta T, Kobayashi Y, Masuda K, Banno K, et al. Lobular endocervical glandular hyperplasia and peritoneal pigmentation associated with Peutz–Jeghers syndrome due to a germline mutation of STK11. Ann Oncol. 2012;23:2990–2.
Anttila A, Ronco G. Description of the national situation of cervical cancer screening in the member states of the European Union. Eur J Cancer. 2009;45:2685–708.
Banno K, Kisu I, Yanokura M, Masuda K, Ueki A, Kobayashi Y, et al. Hereditary gynecological tumors associated with Peutz–Jeghers syndrome (Review). Oncol Lett. 2013;6:1184–8.
Banno K, Kisu I, Yanokura M, Masuda K, Ueki A, Kobayashi Y, et al. Epigenetics and genetics in endometrial cancer: new carcinogenic mechanisms and relationship with clinical practice. Epigenomics. 2012;4:147–62.
Rodu B, Martinez MG Jr. Peutz–Jeghers syndrome and cancer. Oral. Pathology. 1984;58:584–8.
Lele SM, Sawh RN, Zaharopoulos P, Adesokan A, Smith M, Linhart JM, et al. Malignant ovarian sex cord tumor with annular tubules in a patient with Peutz–Jeghers syndrome: a case report. Pathology. 2000;13:466–70.
Barker D, Sharma R, McIndoe A, Blair E, Hall M, Gabra H, et al. An unusual case of sex cord tumor with annular tubules with malignant transformation in a patient with Peutz–Jeghers syndrome. Int J Gynecol Pathol. 2010;29:27–32.
Argento M, Hoffman P, Gauchez AS. Ovarian cancer detection and treatment: current situation and future prospects. Anticancer Res. 2008;28:3135–8.
Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75–89.
Mehenni H, Resta N, Park JG, Miyaki M, Guanti G, Costanza MC. Cancer risks in LKB1 germline mutation carriers. Gut. 2006;55:984–90.
Bosman FT. The hamartoma–adenoma–carcinoma sequence. J Pathol. 1999;188:1–2.
Bouraoui S, Azouz H, Kechrid H, Lemaiem F, Mzabi-Regaya S. Peutz–Jeghers’ syndrome with malignant development in a hamartomatous polyp: report of one case and review of the literature. Gastroenterol Clin Biol. 2008;32:250–4.
Jansen M, de Leng WW, Baas AF, Myoshi H, Mathus-Vliegen L, Taketo MM, et al. Mucosal prolapse in the pathogenesis of Peutz–Jeghers polyposis. Gut. 2006;55:1–5.
Latchford AR, Phillps RK. Gastointestinal polyps and cancer in Peutz–Jeghers syndrome: clinical aspects. Fam Cancer. 2011;10:455–61.
Denost Q, Chafai N, Arrive L, Mourra N, Paye F. Hereditary intraductal papillary mucinous neoplasm of the pancreas. Clin Res Hepatol Gastroenterol. 2012;36:e23–5.
Becker AE, Hernandez YG, Frucht H, Lucas A. Pancreatic ductal adenocarcinoma: risk factors, screening, and early detection. World J Gastroentetol. 2014;30:11182–98.
Korsse SE, Harinck F, van Lier MG, Biermann K, Offerhaus GJ, Krak N, et al. Pancreatic cancer risk in Peutz–Jeghers syndrome patients: a large cohort study and implications for surveillance. J Med Genet. 2013;50:59–64.
Triggiani V, Guastamacchia E, Renzulli G, Giagulli VA, Tafaro E, Licchelli B, et al. Papillary thyroid carcinoma in Peutz–Jeghers syndrome. Thyroid. 2011;21:1273–7.
Boardman LA, Thibodeau SN, Schaid DJ, Lindor NM, McDonnell SK, Burgart LJ, et al. Increased risk for cancer in patients with the Peutz–Jeghers syndrome. Ann Internal Med. 1998;128:896–9.
Zirilli L, Benatti P, Romano S, Roncucci L, Rossi G, Diazzi C, et al. Differentiated thyroid carcinoma (DTC) in a young woman with Peutz–Jeghers syndrome: are these two conditions associated? Exp Clin Endocrinol Diabetes. 2009;117:234–9.
Schumacher V, Vogel T, Leube B, Driemel C, Goecke T, Möslein G, et al. STK11 genotyping and cancer risk in Peutz–Jeghers syndrome. J Med Genet. 2005;42:428–35.
Mehenni H, Resta N, Guanti G, Mota-Vieira L, Lerner A, Peyman M, et al. Molecular and clinical characteristics in 46 families affected with Peutz–Jeghers syndrome. Dig Dis Sci. 2007;52:1924–33.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ishida, H., Tajima, Y., Gonda, T. et al. Update on our investigation of malignant tumors associated with Peutz–Jeghers syndrome in Japan. Surg Today 46, 1231–1242 (2016). https://doi.org/10.1007/s00595-015-1296-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00595-015-1296-y