Peutz‑Jeghers syndrome: Skin manifestations and endocrine anomalies (Review)

Sandru,Florica; Petca,Aida; Dumitrascu,Mihai Cristian; Petca,Razvan-Cosmin; Carsote,Mara

doi:10.3892/etm.2021.10823

Peutz‑Jeghers syndrome: Skin manifestations and endocrine anomalies (Review)

Authors:
- Florica Sandru
- Aida Petca
- Mihai Cristian Dumitrascu
- Razvan-Cosmin Petca
- Mara Carsote
View Affiliations

Affiliations: Department of Dermatology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Obstetrics and Gynecology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Urology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Endocrinology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
Published online on: September 29, 2021 https://doi.org/10.3892/etm.2021.10823
Article Number: 1387

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Peutz‑Jeghers syndrome (PJS), a rare autosomal dominant serine/threonine kinase 11 (STK11)/ liver kinase B1 (LKB1) gene‑related genodermatosis, is characterized by oral hyperpigmentation (OHP); multiple gastro‑intestinal mucosal benign hamartomatous polyps causing local bleeding, occlusion, intussusception, post‑resection small bowel syndrome, associated increased risk of small intestinal cancer (incidence during the third decade); and 76% cumulative higher risk than the global population of developing non‑gastrointestinal tumors (female predominance) including ovarian/testicular neoplasia, pancreatic and gynecologic (breast, uterus, ovarian) cancers. Suggestive PJS‑associated OHP requires STK11 genetic testing. Abdominal pain in an OHP patient may be related to PJS‑associated polyps. Other features include focal depigmentation followed by hyperpigmentation, and xeroderma pigmentosum‑like lesions. The severity of the dermatological findings is correlated with gastrointestinal polyps. The STK11 gene is linked to reserve of primordial follicles, polycystic ovary syndrome, female fertility, and spermatogenesis. PJS is associated with 2 types of ovarian sex‑cord stroma tumors (SCSTs): annular tubules (SCTATs) and pure Sertoli cell tumors. SCSTs accounts for 8% of ovarian cancer and SCTATs represents 2% of SCST, which may be associated with the overproduction of progesterone. PJS‑SCTAT vs. non‑PJS‑SCTAT reveals bilateral/multifocal, small tumors with a benign behavior vs. a unique ovarian, large tumor with increased malignant/metastasis risk. Male precocious puberty is due to large cell calcifying Sertoli cell tumors (LCCSCTs). Notably, 30‑40% of LCCSCTs are caused by PJS or Carney complex. PJS‑LCCSCT is not aggressive, but it may be bilateral/multifocal, with the ultrasound hallmark being micro‑calcifications. Testicular, intra‑tubular large cell hyalinizing Sertoli cell tumor is the second testicle neoplasia in PJS. The skin and mucosal lesions are useful markers of PJS, assisting with the early identification of hamartomatouspolyps and initiation of serial surveillance of ovarian, or testicular neoplasia.

View Figures

View References

1	Nevozinskaya Z, Korsunskaya I, Sakaniya L, Perlamutrov Y and Sobolev V: Peutz-Jeghers syndrome in dermatology. Acta Dermatovenerol Alp Pannonica Adriat. 28:135–137. 2019.PubMed/NCBI
2	Zhang W, Ding Y, Zhang C, Lu Q, Liu Z, Coughlan K, Okon I and Zou MH: Deletion of endothelial cell-specific liver kinase B1 increases angiogenesis and tumor growth via vascular endothelial growth factor. Oncogene. 36:4277–4287. 2017.PubMed/NCBI View Article : Google Scholar
3	Esteve-Puig R, Gil R, González-Sánchez E, Bech-Serra JJ, Grueso J, Hernández-Losa J, Moliné T, Canals F, Ferrer B, Cortés J, et al: A mouse model uncovers LKB1 as an UVB-induced DNA damage sensor mediating CDKN1A (p21WAF1/CIP1) degradation. PLoS Genet. 10(e1004721)2014.PubMed/NCBI View Article : Google Scholar
4	Herrmann JL, Byekova Y, Elmets CA and Athar M: Liver kinase B1 (LKB1) in the pathogenesis of epithelial cancers. Cancer Lett. 306:1–9. 2011.PubMed/NCBI View Article : Google Scholar
5	Zhang Y, Meng Q, Sun Q, Xu ZX, Zhou H and Wang Y: LKB1 deficiency-induced metabolic reprogramming in tumorigenesis and non-neoplastic diseases. Mol Metab. 44(101131)2021.PubMed/NCBI View Article : Google Scholar
6	Syarifuddin E, Masadah R, Lusikooy RE, Warsinggih Uwuratuw JA and Faruk M: Peutz-Jeghers syndrome in a woman presenting as intussusception: A case report. Int J Surg Case Rep. 79:286–290. 2021.PubMed/NCBI View Article : Google Scholar
7	Shrivastava A, Gupta A, Gupta A and Shrivastava J: Unusual presentation of intussusception of the small bowel with peutz jeghers syndrome: Report of a case. J Clin Diagn Res. 7:2296–2297. 2013.PubMed/NCBI View Article : Google Scholar
8	Intratubular Armijo B, Bocklage T and Heideman R: Large cell hyalinizing sertoli cell tumor of the testes in a 4-year-old male with peutz-jeghers syndrome. J Pediatr Hematol Oncol. 37:e184–e187. 2015.PubMed/NCBI View Article : Google Scholar
9	Khanna K, Khanna V and Bhatnagar V: Peutz-Jeghers syndrome: Need for early screening. BMJ Case Rep. 11(e225076)2018.PubMed/NCBI View Article : Google Scholar
10	Tomas C, Soyer P, Dohan A, Dray X, Boudiaf M and Hoeffel C: Update on imaging of Peutz-Jeghers syndrome. World J Gastroenterol. 20:10864–10875. 2014.PubMed/NCBI View Article : Google Scholar
11	Ben Hammouda S, Njima M, Ben Abdeljelil N, Bellalah A, Njim L and Zakhama A: An unusual presentation revealing Peutz-Jeghers syndrome in adult. Ann Med Surg (Lond). 58:87–90. 2020.PubMed/NCBI View Article : Google Scholar
12	Dutta A, Ghosh SK and Kundu SK: Peutz Jegher syndrome. Indian Pediatr. 52:176–177. 2015.PubMed/NCBI
13	Tacheci I, Kopacova M and Bures J: Peutz-Jeghers syndrome. Curr Opin Gastroenterol. 37:245–254. 2021.PubMed/NCBI View Article : Google Scholar
14	Kidambi TD, Kohli DR, Samadder NJ and Singh A: Hereditary polyposis syndromes. Curr Treat Options Gastroenterol. 17:650–665. 2019.PubMed/NCBI View Article : Google Scholar
15	Shah KR, Boland CR, Patel M, Thrash B and Menter A: Cutaneous manifestations of gastrointestinal disease: Part I. J Am Acad Dermatol. 68:211.e1–e33. 2013.PubMed/NCBI View Article : Google Scholar
16	Shen Z, Hoffman JD, Hao F and Pier E: More than just skin deep: Faciocutaneous clues to genetic syndromes with malignancies. Oncologist. 17:930–936. 2012.PubMed/NCBI View Article : Google Scholar
17	Patel LM, Lambert PJ, Gagna CE, Maghari A and Lambert WC: Cutaneous signs of systemic disease. Clin Dermatol. 29:511–522. 2011.PubMed/NCBI View Article : Google Scholar
18	Duan N, Zhang YH, Wang WM and Wang X: Mystery behind labial and oral melanotic macules: Clinical, dermoscopic and pathological aspects of Laugier-Hunziker syndrome. World J Clin Cases. 6:322–334. 2018.PubMed/NCBI View Article : Google Scholar
19	Lehmann AR, McGibbon D and Stefanini M: Xeroderma pigmentosum. Orphanet J Rare Dis. 6(70)2011.PubMed/NCBI View Article : Google Scholar
20	Vageli DP, Doukas SG and Markou A: Mismatch DNA repair mRNA expression profiles in oral melanin pigmentation lesion and hamartomatous polyp of a child with Peutz-Jeghers syndrome. Pediatr Blood Cancer. 60:E116–E117. 2013.PubMed/NCBI View Article : Google Scholar
21	Zhang Y, Ke Y, Zheng X, Liu Q and Duan X: Correlation between genotype and phenotype in three families with Peutz-Jeghers Syndrome. Exp Ther Med. 13:507–514. 2017.PubMed/NCBI View Article : Google Scholar
22	Duong BT and Winship I: The role of STK 11 gene testing in individuals with oral pigmentation. Australas J Dermatol. 58:135–138. 2017.PubMed/NCBI View Article : Google Scholar
23	Chan TC and Sirlin C: Abdominal pain in a young man with oral pigmentations. J Emerg Med. 50:335–336. 2016.PubMed/NCBI View Article : Google Scholar
24	Wagner A, Aretz S, Auranen A, Bruno MJ, Cavestro GM, Crosbie EJ, Goverde A, Jelsig AM, Latchford A, Leerdam MEV, et al: The Management of peutz-jeghers syndrome: European hereditary tumour group (EHTG) guideline. J Clin Med. 10(473)2021.PubMed/NCBI View Article : Google Scholar
25	Sputa-Grzegrzolka P, Wozniak Z, Akutko K, Pytrus T, Baran W, Calik J, Glatzel-Plucinska N, Domagala Z, Podhorska-Okolow M, Stawarski A and Dziegiel P: Laugier-Hunziker syndrome: A case report of the pediatric patient and review of the literature. Int J Dermatol. 59:1513–1519. 2020.PubMed/NCBI View Article : Google Scholar
26	Lause M, Kamboj A and Fernandez Faith E: Dermatologic manifestations of endocrine disorders. Transl Pediatr. 6:300–312. 2017.PubMed/NCBI View Article : Google Scholar
27	Legrand MA, Raverot G, Nicolino M and Chapurlat R: GNAS mutated thyroid carcinoma in a patient with Mc Cune Albright syndrome. Bone Rep. 13(100299)2020.PubMed/NCBI View Article : Google Scholar
28	Sandru F, Carsote M, Valea A, Albu SE, Petca RC and Dumitrascu MC: Somatostatinoma: Beyond neurofibromatosis type 1 (Review). Exp Ther Med. 20:3383–3388. 2020.PubMed/NCBI View Article : Google Scholar
29	Wang WM, Wang X, Duan N, Jiang HL and Huang XF: Laugier-Hunziker syndrome: A report of three cases and literature review. Int J Oral Sci. 4:226–230. 2012.PubMed/NCBI View Article : Google Scholar
30	Lalosevic J, Zivanovic D, Skiljevic D and Medenica L: Laugier-Hunziker syndrome-Case report. An Bras Dermatol. 90 (3 Suppl 1):S223–S225. 2015.PubMed/NCBI View Article : Google Scholar
31	Wei Z, Li GY, Ruan HH, Zhang L, Wang WM and Wang X: Laugier-Hunziker syndrome: A case report. J Stomatol Oral Maxillofac Surg. 119:158–160. 2018.PubMed/NCBI View Article : Google Scholar
32	Cusick EH, Marghoob AA and Braun RP: Laugier-Hunziker syndrome: A case of asymptomatic mucosal and acral hyperpigmentation. Dermatol Pract Concept. 7:27–30. 2017.PubMed/NCBI View Article : Google Scholar
33	Rangwala S, Doherty CB and Katta R: Laugier-Hunziker syndrome: A case report and review of the literature. Dermatol Online J. 16(9)2010.PubMed/NCBI
34	Leung AKC, Lam JM, Leong KF and Sergi CM: Melanonychia striata: Clarifying behind the Black Curtain. A review on clinical evaluation and management of the 21st century. Int J Dermatol. 58:1239–1245. 2019.PubMed/NCBI View Article : Google Scholar
35	Miličević T, Žaja I, Tešanović D and Radman M: Laugier-Hunziker syndrome in endocrine clinical practice. Endocrinol Diabetes Metab Case Rep:. 2018:18–0025. 2018.PubMed/NCBI View Article : Google Scholar
36	Wilder EG, Frieder J, Sulhan S, Michel P, Cizenski JD, Wright JM and Menter MA: Spectrum of orocutaneous disease associations: Genodermatoses and inflammatory conditions. J Am Acad Dermatol. 77:809–830. 2017.PubMed/NCBI View Article : Google Scholar
37	Babu NA, Rajesh E, Krupaa J and Gnananandar G: Genodermatoses. J Pharm Bioallied Sci. 7 (Suppl 1):S203–S206. 2015.PubMed/NCBI View Article : Google Scholar
38	Pinna R, Cocco F, Campus G, Conti G, Milia E, Sardella A and Cagetti MG: Genetic and developmental disorders of the oral mucosa: Epidemiology; molecular mechanisms; diagnostic criteria; management. Periodontol 2000. 80:12–27. 2019.PubMed/NCBI View Article : Google Scholar
39	Kennedy RA, Thavaraj S and Diaz-Cano S: An overview of autosomal dominant tumour syndromes with prominent features in the oral and maxillofacial region. Head Neck Pathol. 11:364–376. 2017.PubMed/NCBI View Article : Google Scholar
40	Sandru F, Carsote M, Albu SE, Valea A, Petca A and Dumitrascu MC: Glucagonoma: From skin lesions to the neuroendocrine component (Review). Exp Ther Med. 20:3389–3393. 2020.PubMed/NCBI View Article : Google Scholar
41	Stratakis CA: Hereditary syndromes predisposing to endocrine tumors and their skin manifestations. Rev Endocr Metab Disord. 17:381–388. 2016.PubMed/NCBI View Article : Google Scholar
42	Ponti G, Tomasi A, Manfredini M and Pellacani G: Oral mucosal stigmata in hereditary-cancer syndromes: From germline mutations to distinctive clinical phenotypes and tailored therapies. Gene. 582:23–32. 2016.PubMed/NCBI View Article : Google Scholar
43	Lodish MB and Stratakis CA: The differential diagnosis of familial lentiginosis syndromes. Fam Cancer. 10:481–490. 2011.PubMed/NCBI View Article : Google Scholar
44	Ferreira LDS, Calderipe CB, Maass JB, Carrard VC, Martins MD, Abreu LG, Shuch LF and Uchoa Vasconcelos AC: Oral pigmented lesions in syndromic individuals: A systematic review. Oral Dis: Jan 4, 2021 (Epub ahead of print).
45	Ueki A and Hirasawa A: Molecular features and clinical management of hereditary gynecological cancers. Int J Mol Sci. 21(9504)2020.PubMed/NCBI View Article : Google Scholar
46	Pietragalla A, Arcieri M, Marchetti C, Scambia G and Fagotti A: Ovarian cancer predisposition beyond BRCA1 and BRCA2 genes. Int J Gynecol Cancer. 30:1803–1810. 2020.PubMed/NCBI View Article : Google Scholar
47	Chung SH, Woldenberg N, Roth AR, Masamed R, Conlon W, Cohen JG, Joines MM and Patel MK: BRCA and Beyond: Comprehensive image-rich review of hereditary breast and gynecologic cancer syndromes. Radiographics. 40:306–325. 2020.PubMed/NCBI View Article : Google Scholar
48	Jiang ZZ, Hu MW, Ma XS, Schatten H, Fan HY, Wang ZB and Sun QY: LKB1 acts as a critical gatekeeper of ovarian primordial follicle pool. Oncotarget. 7:5738–5753. 2016.PubMed/NCBI View Article : Google Scholar
49	Smith KJ and Germain M: Polycystic ovary syndrome (PCOS) with melanocytic mucosal macules: The role of STK11 gene polymorphisms in PCOS and Peutz-Jeghers syndrome. Int J Dermatol. 55:177–180. 2016.PubMed/NCBI View Article : Google Scholar
50	Gheorghisan-Galateanu AA, Carsote M, Terzea D, Valea A and Ghemigian A: Ovarian Sertoli cell tumours: Practical points. J Pak Med Assoc. 70:129–133. 2020.PubMed/NCBI View Article : Google Scholar
51	Garg K, Karnezis AN and Rabban JT: Uncommon hereditary gynaecological tumour syndromes: Pathological features in tumours that may predict risk for a germline mutation. Pathology. 50:238–256. 2018.PubMed/NCBI View Article : Google Scholar
52	Fuller PJ, Leung D and Chu S: Genetics and genomics of ovarian sex cord-stromal tumors. Clin Genet. 91:285–291. 2017.PubMed/NCBI View Article : Google Scholar
53	Weissman SM, Weiss SM and Newlin AC: Genetic testing by cancer site: Ovary. Cancer J. 18:320–327. 2012.PubMed/NCBI View Article : Google Scholar
54	Jaegle WT, Keyser EA, Messersmith L, Brady RO and Miller C: Extraovarian sex cord tumor with annular tubules discovered arising from a leiomyoma. Gynecol Oncol Rep. 26:17–20. 2018.PubMed/NCBI View Article : Google Scholar
55	Young RH: Ovarian sex cord-stromal tumours and their mimics. Pathology. 50:5–15. 2018.PubMed/NCBI View Article : Google Scholar
56	Plevová P and Geržová H: Genetic causes of rare pediatric ovarian tumors. Klin Onkol. 32 (Suppl 2):S79–S91. 2019.PubMed/NCBI View Article : Google Scholar
57	Yahaya JJ, Mshana D and Mremi A: Ovarian sex cord tumour with annular tubules in a 13-year-old female: A case report. Oxf Med Case Reports. 2020(omaa024)2020.PubMed/NCBI View Article : Google Scholar
58	Choudhary F, Tanveer N, Mangla G and Gayatree A: Non-syndromic sex cord tumor with annular tubules: A rare diagnosis. Indian J Surg Oncol. 11:313–315. 2020.PubMed/NCBI View Article : Google Scholar
59	Han Y, Li S, Wu L, Zhang X and Cao D: Non-Peutz-Jeghers syndrome-associated ovarian sex cord tumor with annular tubules: Report of a malignant case. J Obstet Gynaecol Res. 42:224–227. 2016.PubMed/NCBI View Article : Google Scholar
60	Ravishankar S, Mangray S, Kurkchubasche A, Yakirevich E and Young RH: Unusual sertoli cell tumor associated with sex cord tumor with annular tubules in peutz-jeghers syndrome: Report of a case and review of the literature on ovarian tumors in peutz-jeghers syndrome. Int J Surg Pathol. 24:269–273. 2016.PubMed/NCBI View Article : Google Scholar
61	Kwon SY, Choe MS, Lee HW, Lee HJ, Shin SJ and Cho CH: Minimal deviation adenocarcinoma of the cervix and tumorlets of sex-cord stromal tumor with annular tubules of the ovary in Peutz-Jeghers syndrome. J Gynecol Oncol. 24:92–95. 2013.PubMed/NCBI View Article : Google Scholar
62	Singh M, Mandal S and Majumdar K: Sex cord tumor with annular tubules: An incidental finding in an endometriotic cyst-the first known co-occurrence. Biomed Res Int. 2014(970243)2014.PubMed/NCBI View Article : Google Scholar
63	Howell L, Bader A, Mullassery D, Losty P, Auth M and Kokai G: Sertoli Leydig cell ovarian tumour and gastric polyps as presenting features of Peutz-Jeghers syndrome. Pediatr Blood Cancer. 55:206–207. 2010.PubMed/NCBI View Article : Google Scholar
64	Poiana C, Virtej I, Carsote M, Banceanu G, Sajin M, Stanescu B, Ioachim D, Hortopan D and Coculescu M: Virilising Sertoli-Leydig cell tumour associated with thyroid papillary carcinoma: Case report and general considerations. Gynecol Endocrinol. 26:617–622. 2010.PubMed/NCBI View Article : Google Scholar
65	Bellfield EJ and Alemzadeh R: Recurrent ovarian Sertoli-Leydig cell tumor in a child with Peutz-Jeghers syndrome. Oxf Med Case Reports. 2016(omw048)2016.PubMed/NCBI View Article : Google Scholar
66	Kong F, Wang M, Huang X, Yue Q, Wei X, Dou X, Peng X, Jia Y, Zheng K, Wu T, et al: Differential regulation of spermatogenic process by Lkb1 isoforms in mouse testis. Cell Death Dis. 8(e3121)2017.PubMed/NCBI View Article : Google Scholar
67	Valeri C, Lovaisa MM, Racine C, Edelsztein NY, Riggio M, Giulianelli S, Venara M, Bedecarrás P, Ballerini MG, di Clemente N, et al: Molecular mechanisms underlying AMH elevation in hyperoestrogenic states in males. Sci Rep. 10(15062)2020.PubMed/NCBI View Article : Google Scholar
68	Zhang LJ, Su Z, Liu X, Wang L and Zhang Q: Peutz-Jeghers syndrome with early onset of pre-adolescent gynecomastia: A predigree case report and clinical and molecular genetic analysis. Am J Transl Res. 9:2639–2644. 2017.PubMed/NCBI
69	Renes JS, Knijnenburg J, Chitoe-Ramawadhdoebe S, Gille JJP, de Bruin C and Barge-Schaapveld DQCM: Possible hints and pitfalls in diagnosing Peutz-Jeghers syndrome. J Pediatr Endocrinol Metab. 31:1381–1386. 2018.PubMed/NCBI View Article : Google Scholar
70	Kaluzny A, Matuszewski M, Wojtylak S, Krajka K, Cichy W, Plawski A, Gintowt A and Lipska BS: Organ-sparing surgery of the bilateral testicular large cell calcifying Sertoli cell tumor in patient with atypical Peutz-Jeghers syndrome. Int Urol Nephrol. 44:1045–1048. 2012.PubMed/NCBI View Article : Google Scholar
71	Tracey AJ and Cerwinka WH: Benign large-cell calcifying sertoli tumor of the testis in a 13-year-old male patient treated with partial orchiectomy. Urology. 107:226–228. 2017.PubMed/NCBI View Article : Google Scholar
72	Simões-Pereira J, Santos F, Lopes L and Limbert C: Prepubertal gynaecomastia in a boy with Peutz-Jeghers syndrome: Managing the aromatase overexpression. J Pediatr Endocrinol Metab. 31:1149–1154. 2018.PubMed/NCBI View Article : Google Scholar
73	Gourgari E, Saloustros E and Stratakis CA: Large-cell calcifying Sertoli cell tumors of the testes in pediatrics. Curr Opin Pediatr. 24:518–522. 2012.PubMed/NCBI View Article : Google Scholar
74	Pelit ES, Erol B, Zenginkinet T and Çaşkurlu T: Testis-sparing surgery of unilateral testicular large-cell calcifying Sertoli cell tumor: A sporadic case. Turk J Urol. 44:370–372. 2018.PubMed/NCBI View Article : Google Scholar
75	Koç Yekedüz M, Şıklar Z, Burgu B, Kuloğlu Z, Kocaay P, Çamtosun E, İsakoca M, Kansu A, Soygür T and Berberoğlu M: Response to anastrozole treatment in a case with peutz-jeghers syndrome and a large cell calcifying Sertoli cell tumor. Clin Res Pediatr Endocrinol. 9:168–171. 2017.PubMed/NCBI View Article : Google Scholar
76	Crocker MK, Gourgari E, Lodish M and Stratakis CA: Use of aromatase inhibitors in large cell calcifying sertoli cell tumors: Effects on gynecomastia, growth velocity, and bone age. J Clin Endocrinol Metab. 99:E2673–E2680. 2014.PubMed/NCBI View Article : Google Scholar
77	Idrees MT, Ulbright TM, Oliva E, Young RH, Montironi R, Egevad L, Berney D, Srigley JR, Epstein JI and Tickoo SK: Members of the international society of urological pathology testicular tumour panel. The World Health Organization 2016 classification of testicular non-germ cell tumours: A review and update from the International Society of Urological Pathology Testis Consultation Panel. Histopathology. 70:513–521. 2017.PubMed/NCBI View Article : Google Scholar
78	Cauchin E, Touchefeu Y and Matysiak-Budnik T: Hamartomatous tumors in the gastrointestinal tract. Gastrointest Tumors. 2:65–74. 2015.PubMed/NCBI View Article : Google Scholar
79	Rosty C: The Role of the surgical pathologist in the diagnosis of gastrointestinal polyposis syndromes. Adv Anat Pathol. 25:1–13. 2018.PubMed/NCBI View Article : Google Scholar
80	Suzuki K, Higuchi H, Shimizu S, Nakano M, Serizawa H and Morinaga S: Endoscopic snare papillectomy for a solitary Peutz-Jeghers-type polyp in the duodenum with ingrowth into the common bile duct: Case report. World J Gastroenterol. 21:8215–8220. 2015.PubMed/NCBI View Article : Google Scholar
81	Endo K, Kawamura K, Murakami K, Murakami K, Nagao M, Satoh T, Takasu A, Kogure T, Hirota M, Meguro T, et al: A case of jejunal solitary Peutz-Jeghers polyp with intussusception identified by double-balloon enteroscopy. Clin J Gastroenterol. 13:1129–1135. 2020.PubMed/NCBI View Article : Google Scholar
82	Kumar S, Arora P and Goswami P: Recurrent intestinal obstruction in a patient of Peutz-Jeghers syndrome. J Cancer Res Ther. 15:252–254. 2019.PubMed/NCBI View Article : Google Scholar
83	Mărginean CO, Meliţ LE, Patraulea F, Iunius S and Mărginean MO: Early onset Peutz-Jeghers syndrome, the importance of appropriate diagnosis and follow-up: A case report. Medicine (Baltimore). 98(e16381)2019.PubMed/NCBI View Article : Google Scholar
84	Duan SX, Wang GH, Zhong J, Ou WH, Fu MX, Wang FS, Ma SH and Li JH: Peutz-Jeghers syndrome with intermittent upper intestinal obstruction: A case report and review of the literature. Medicine (Baltimore). 96(e6538)2017.PubMed/NCBI View Article : Google Scholar
85	Rodríguez Lagos FA, Sorlí Guerola JV, Romero Martínez IM and Codoñer Franch P: Register and clinical follow-up of patients with Peutz-Jeghers syndrome in Valencia. Rev Gastroenterol Mex. 85:123–139. 2020.PubMed/NCBI View Article : Google Scholar
86	De Latour RA, Kilaru SM and Gross SA: Management of small bowel polyps: A literature review. Best Pract Res Clin Gastroenterol. 31:401–408. 2017.PubMed/NCBI View Article : Google Scholar
87	Achatz MI, Porter CC, Brugières L, Druker H, Frebourg T, Foulkes WD, Kratz CP, Kuiper RP, Hansford JR, Hernandez HS, et al: Cancer screening recommendations and clinical management of inherited gastrointestinal cancer syndromes in childhood. Clin Cancer Res. 23:e107–e114. 2017.PubMed/NCBI View Article : Google Scholar
88	Shaco-Levy R, Jasperson KW, Martin K, Samadder NJ, Burt RW, Ying J and Bronner MP: Morphologic characterization of hamartomatous gastrointestinal polyps in Cowden syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Hum Pathol. 49:39–48. 2016.PubMed/NCBI View Article : Google Scholar
89	Linhart H, Bormann F, Hutter B, Brors B and Lyko F: Genetic and epigenetic profiling of a solitary Peutz-Jeghers colon polyp. Cold Spring Harb Mol Case Stud. 3(a001610)2017.PubMed/NCBI View Article : Google Scholar
90	Li T, Lin W, Zhao Y, Zhu J, Sun T and Ren L: Distinct promoter methylation patterns of LKB1 in the hamartomatous polyps of Peutz-Jeghers syndrome and its potential in gastrointestinal malignancy prediction. Orphanet J Rare Dis. 15(208)2020.PubMed/NCBI View Article : Google Scholar
91	Wang Z, Wu B, Mosig RA, Chen Y, Ye F, Zhang Y, Gong W, Gong L, Huang F, Wang X, et al: STK11 domain XI mutations: Candidate genetic drivers leading to the development of dysplastic polyps in Peutz-Jeghers syndrome. Hum Mutat. 35:851–858. 2014.PubMed/NCBI View Article : Google Scholar
92	Jedrzkiewicz J, Quencer K, Matynia AP, Morrow E, Pletneva M and Barraza G: Peutz-jeghers type polyp of the appendix with review of literature. Case Rep Pathol. 2019(7584070)2019.PubMed/NCBI View Article : Google Scholar
93	Zhang Z, Duan FX, Gu GL and Yu PF: Mutation analysis of related genes in hamartoma polyp tissue of Peutz-Jeghers syndrome. World J Gastroenterol. 26:1926–1937. 2020.PubMed/NCBI View Article : Google Scholar
94	Jung I, Gurzu S and Turdean GS: Current status of familial gastrointestinal polyposis syndromes. World J Gastrointest Oncol. 7:347–355. 2015.PubMed/NCBI View Article : Google Scholar
95	Yu Q, Subedi S, Tong Y, Wei Q, Xu H, Wang Y, Gong Y and Shi Y: Scalp metastases as first presentation of pulmonary adenocarcinomas: A case report. Onco Targets Ther. 11:6147–6151. 2018.PubMed/NCBI View Article : Google Scholar
96	Zaba O, Holbe D, Aretz S and Grohé C: LKB1 mutant in a KRAS activated adenocarcinoma of the lung associated with Peutz-Jeghers syndrome: A case report. Lung Cancer. 82:368–369. 2013.PubMed/NCBI View Article : Google Scholar
97	Osoegawa A, Kometani T, Nosaki K, Ondo K, Hamatake M, Hirai F, Seto T, Sugio K and Ichinose Y: LKB1 mutations frequently detected in mucinous bronchioloalveolar carcinoma. Jpn J Clin Oncol. 41:1132–1137. 2011.PubMed/NCBI View Article : Google Scholar
98	Kojima Y, Ohtsuka K, Ishii S, Aso N, Ohki A, Hashimoto Y, Takeuchi H, Ohnishi H and Abe N: STK11. p. F354L germline mutation in a case of multiple gastrointestinal tumors. Case Rep Gastroenterol. 14:547–553. 2020.PubMed/NCBI View Article : Google Scholar
99	Boda D: Cellomics as integrative omics for cancer. Curr Proteomics. 10:237–245. 2013.
100	Neagu M, Constantin C, Tanase C and Boda D: Patented biomarker panels in early detection of cancer. Recent Patents Biomarkers. 1:10–14. 2011.
101	Lupu M, Caruntu A, Caruntu C, Papagheorghe LML, Ilie MA, Voiculescu V, Boda D, Constantin C, Tanase C, Sifaki M, et al: Neuroendocrine factors: The missing link in non melanoma skin cancer. Oncol Rep. 38:1327–1340. 2017.PubMed/NCBI View Article : Google Scholar