Metachronous Breast and Lung Cancers in a Middle-Aged Woman with Peutz-Jeghers Syndrome

• Kenji Ina

  Department of Geriatric Medicine, Shinseikai Dai-ichi Hospital, Japan

  https://orcid.org/0000-0001-8646-0611

• Mikinori Miyazaki

  Department of Respiratory Medicine, Nagoya Memorial Hospital, Japan

• Tomoko Nishio

  Department of Pathology, Nagoya Memorial Hospital, Japan

• Yuko Kato

  Medical Social Work Consultation Room, Nagoya Memorial Hospital, Japan

• Satoshi Kayukawa

  Department of Clinical Oncology, Nagoya Memorial Hospital, Japan

• Takae Kataoka

  Department of Clinical Oncology, Nagoya Memorial Hospital, Japan

• Katsuhiko Endo

  Department of Surgery, Nagoya Memorial Hospital, Japan

• Tomoki Fukuoka

  Department of Surgery, Nagoya Memorial Hospital, Japan

We report the case of a middle-aged woman with Peutz-Jeghers syndrome who developed metachronous breast and lung cancers, because lung cancer is infrequently associated with PJS, especially for women with this disorder. At the age of 12 years, the patient was diagnosed with Peutz-Jeghers syndrome owing to the presence of multiple hamartomatous polyps in the gastrointestinal tract and mucocutaneous melanin pigmentation. She developed breast cancer and underwent curative mastectomy and postoperative adjuvant chemotherapy at 48 years of age. Five years later, computed tomography showed multiple lung nodules. The pathological diagnosis of the lung lesion was a mucinous adenocarcinoma, which differed from that of the resected breast cancer. She then received cisplatin/ pemetrexed therapy combined with pembrolizumab for non-small cell lung cancer, which reduced the size of the lung tumors. However, the disease eventually progressed, and she underwent a gene panel test because of the refractoriness to pharmacotherapy, which demonstrated a germline STK11 pathogenic variant.

Wagner A, Aretz S, Auranen A, et al. The management of Peutz-Jeghers syndrome: European Hereditary Tumor Group (EHTG) Guideline. J Clin Med 2021; 10: 473. https://doi.org/10.3390/jcm10030473

Tomlinson IP, Houlston RS. Peutz-Jeghers syndrome. J Med Genet 1997; 34: 1007-1011. https://doi.org/10.1136/jmg.34.12.1007

Amru R, Dhok A. Peutz-Jeghers Syndrome: A Comprehensive Review of Genetics, Clinical Features, and Management Approaches. Cureus 2024; 16: e58887. https://doi.org/10.7759/cureus.58887

Zyla RE, Hahn E, Hodgson A. Gene of the month: STK11. J Clin Pathol 2021; 74: 681-685. https://doi.org/10.1136/jclinpath-2021-207906

Hearle N, Schumacher V, Menko FH, et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 2006; 12: 3209-3215. https://doi.org/10.1158/1078-0432.CCR-06-0083

Giardiello FM, Trimbath JD. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 2006; 4: 408-415. https://doi.org/10.1016/j.cgh.2005.11.005

Klimkowski S, Ibrahim M, Rovira JJI, et al. Peutz-Jeghers syndrome and the role of imaging: pathophysiology, diagnosis, and associated cancers. Cancers 2021; 13: 5121. https://doi.org/10.3390/cancers13205121

Ishida H, Ishida Y, Gonda T, et al. Update on our investigation of malignant tumors associated with Peutz-Jeghers syndrome in Japan. Surg Today 2016; 46: 1231-1242. https://doi.org/10.1007/s00595-015-1296-y

Wang Z, Wang Z, Wang Y, et al. High risk and early onset of cancer in Chinese patients with Peutz-Jeghers syndrome. Front Oncol 2022; 12: 900516. https://doi.org/10.3389/fonc.2022.900516

Hirano S, Takiguchi Y, Igari H, et al. A case of pulmonary adenocarcinoma accompanied by superior vena caval thrombosis in a patient with Peuz-Jeghers syndrome. Jpn J Clin Oncol 2002; 32: 307-309. https://doi.org/10.1093/jjco/hyf063

von Herbay A, Arens N, Friedl W, et al. Bronchioalveolar carcinoma: a new cancer in Peuz-Jeghers syndrome. Lung Cancer 2005; 47: 283-288. https://doi.org/10.1016/j.lungcan.2004.06.015

Li M-H, Shen J, Zhong B, et al. Peutz-Jeghers syndrome complicated with pulmonary mucinous adenocarcinoma: a case report and review of the literature. Zhonghua Jie He He Hu Xi Za Zhi 2011; 34: 919-922 [Article in Chinese].

Zaba O, Holbe D, Aretz S, et al. LKB1 mutant in a KRAS activated adenocarcinoma of the lung associated with Peutz-Jeghers syndrome: A case report. Lung Cancer 2013; 82: 368-369. https://doi.org/10.1016/j.lungcan.2013.08.019

Yu Q, Subedi S, Tong Y, et al. Scalp metastases as first presentation of pulmonary adenocarcinomas: a case report. Onco Targets Ther 2018; 11: 6147-6151. https://doi.org/10.2147/OTT.S174577

Fostira F, Fountzilas E, Papadopoulou K, et al. Lung cancer as a predominant feature in a patient with Peutz-Jeghers syndrome: Case report. Thorac Cancer 2022; 12: 1862-1865. https://doi.org/10.1111/1759-7714.14447

Osoegawa A, Kometani T, Nosaki K, et al. LKB1 mutations frequently detected in mucinous bronchioloalveolar carcinoma. Jpn J Clin Oncol 2011; 41: 1132-1137. https://doi.org/10.1093/jjco/hyr102

Hemminki A, Markie D, Tomlinson I, et al. A serine/ threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 1998; 391: 184-187. https://doi.org/10.1038/34432

Matsumoto S, Iwakawa R, Takahashi K, et al. Prevalence and specificity of LKB1 genetic alterations in lung cancers. Oncogene 2007; 26: 5911-5918. https://doi.org/10.1038/sj.onc.1210418

Skoulidis F, Goldberg NE, Greenawalt DM, et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov 2018; 8: 822-835. https://doi.org/10.1158/2159-8290.CD-18-0099

Laderian B, Mundi P, Fojo T, et al. Emerging therapeutic implications of STK11 mutation: Case series. Oncologist 2020; 25: 733-737. https://doi.org/10.1634/theoncologist.2019-0846

Vogt A, Schmid S, Heinmann K, et al. Multiple primary tumours: challenges and approaches, a review. ESMO Open 2017; 2: e000172. https://doi.org/10.1136/esmoopen-2017-000172

Tanjak P, Suktitipat B, Vorasan N, et al. Risks and cancer associations of metachronous and synchronous multiple primary cancers: a 25-year retorospective study. BMC Cancer 2021; 21: 1045. https://doi.org/10.1186/s12885-021-08766-9

• PDF

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.