Skip to main content

Advertisement

SpringerLink
Log in

Pancreatic ductal adenocarcinoma with mismatch repair deficiency resected after long-term observation

  • Case Report
  • Published:
Clinical Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Pancreatic ductal adenocarcinoma (PDAC) with mismatch repair (MMR) deficiency is a rare subtype, clinicopathological features of which have not been fully understood. A 70-year-old woman was admitted for the investigation of a 20-mm pancreatic tumor in the pancreatic head, detected during the cause scrutiny of exacerbation of diabetes mellitus and panhypopituitarism. The tumor decreased in size after administration of hydrocortisone for panhypopituitarism. Autoimmune pancreatitis, complicated with hypophysitis, was suspected, and prednisolone treatment was administered. The tumor did not show enlargement for 3 years during which a dose of prednisolone was maintained. However, 1.5 years after the cessation of prednisolone administration, the tumor size increased again. On endoscopic ultrasonography, the tumor was found to be a 25.2-mm mass lesion with almost uniformly low echogenicity and blood flow signal, and anisonucleosis on cytodiagnosis was revealed. Pancreatoduodenectomy was performed, and on histological analysis, moderately differentiated tubular adenocarcinoma with massive lymphocytic infiltration was observed. Immunohistochemistry revealed a concomitant loss of MSH2 and MSH6 in the tumor cells, which implicated mutant MSH2 gene. She has remained well with no recurrence for 2.9 years since her surgery. We herein report a case of PDAC with MMR deficiency, resected after long-term observation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig.12

Similar content being viewed by others

References

  1. Sener SF, Fremgen A, Menck HR, et al. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the National Cancer Database. J Am Coll Surg. 1999;189:1–7.

    Article  CAS  Google Scholar 

  2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.

    Article  Google Scholar 

  3. Simard EP, Ward EM, Siegel R, et al. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin. 2012;62:118–28.

    Article  Google Scholar 

  4. Groot VP, Rezaee N, Wu W, et al. Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2018;267:936–45.

    Article  Google Scholar 

  5. Wagner M, Redaelli C, Lietz M, et al. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91:586–94.

    Article  CAS  Google Scholar 

  6. Connor AA, Denroche RE, Jang GH, et al. Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma. JAMA Oncol. 2017;3:774–83.

    Article  Google Scholar 

  7. Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531:47–52.

    Article  CAS  Google Scholar 

  8. Witkiewicz AK, McMillan EA, Balaji U, Baek G, Lin WC, Mansour J, et al. Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nat Commun. 2015;6:6744.

    Article  CAS  Google Scholar 

  9. Humphris JL, Patch AM, Nones K, et al. Hypermutation in pancreatic cancer. Gastroenterology. 2017;152:68–74.

    Article  CAS  Google Scholar 

  10. Cloyd JM, Katz MHG, Wang H, et al. Clinical and genetic implications of DNA mismatch repair deficiency in patients with pancreatic ductal adenocarcinoma. JAMA Surg. 2017;152:1086–8.

    Article  Google Scholar 

  11. Chetty R. Gastrointestinal cancers accompanied by a dense lymphoid component: an overview with special reference to gastric and colonic medullary and lymphoepithelioma-like carcinomas. J Clin Pathol. 2012;65:1062–5.

    Article  Google Scholar 

  12. Hu ZI, Shia J, Stadler ZK, et al. Evaluating mismatch repair deficiency in pancreatic adenocarcinoma: challenges and recommendations. Clin Cancer Res. 2018;24:1326–36.

    Article  CAS  Google Scholar 

  13. Moon SH, Kim MH, Park DH, et al. Is a 2-week steroid trial after initial negative investigation for malignancy useful in differentiating autoimmune pancreatitis from pancreatic cancer? A prospective outcome study. Gut. 2008;57:1704–12.

    Article  CAS  Google Scholar 

  14. Vijayakumar A, Vijayakumar A. Imaging of focal autoimmune pancreatitis and differentiating it from pancreatic cancer. ISRN Radiol. 2013;2013:569489.

    Google Scholar 

  15. van der Vliet HJ, Perenboom RM. Multiple pseudo tumors in lgG4-associated multifocal systemic fibrosis. Ann lntern Med. 2004;141:896–7.

    Article  Google Scholar 

  16. Shimatsu A, Oki Y, Fujisawa I, et al. Pituitary and stalk lesions (infundibulo-hypophysitis) associated with immunoglobulin G4-related systemic disease: an emerging clinical entity. Endocr J. 2009;56:1033–41.

    Article  Google Scholar 

  17. Nakata B, Wang YQ, Yashiro M, et al. Prognostic value of microsatellite instability in resectable pancreatic cancer. Clin Cancer Res. 2002;8:2536–40.

    CAS  Google Scholar 

  18. Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis. Pancreas. 2011;40:352–8.

    Article  Google Scholar 

  19. Hart PA, Zen Y, Chari ST, et al. Recent advances in autoimmune pancreatitis. Gastroenterology. 2015;149:39–51.

    Article  CAS  Google Scholar 

  20. Okamoto A, Watanabe T, Kamata K, et al. Recent updates on the relationship between cancer and autoimmune pancreatitis. Intern Med. 2019;58:1533–9.

    Article  Google Scholar 

  21. Fraune C, Burandt E, Simon R, et al. MMR Deficiency is Homogeneous in pancreatic carcinoma and associated with high density of Cd8-positive lymphocytes. Ann Surg Oncol. 2020. https://doi.org/10.1245/s10434-020-08209-y [Epub ahead of print].

    Article  Google Scholar 

  22. Smyrk TC, Watson P, Kaul K, et al. Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma. Cancer. 2001;91:2417–22.

    Article  CAS  Google Scholar 

  23. Buckowitz A, Knaebel HP, Benner A, et al. Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastases. Br J Cancer. 2005;92:1746–53.

    Article  CAS  Google Scholar 

  24. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.

    Article  CAS  Google Scholar 

  25. Li GM. Mechanisms and functions of DNA mismatch repair. Cell Res. 2008;18:85–988.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan

    Nobuhiko Ogasawara, Tsunao Imamura, Rikako Koyama, Daisuke Hattori, Yasuo Ito, Yoshiki Sato & Tetsuo Tamura

  2. Department of Pathology, Toranomon Hospital, Tokyo, Japan

    Naoko Inoshita & Atsuhito Nakayama

  3. Department of Gastrointestinal Surgery, Toranomon Hospital, Tokyo, Japan

    Masaji Hashimoto

Authors
  1. Nobuhiko Ogasawara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tsunao Imamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rikako Koyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naoko Inoshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Atsuhito Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daisuke Hattori
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasuo Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yoshiki Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tetsuo Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Masaji Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tsunao Imamura.

Ethics declarations

Conflict of interest

All authors declare that they have no conflicts of interest.

Human/animal rights

All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from the patient for being included in this case report.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ogasawara, N., Imamura, T., Koyama, R. et al. Pancreatic ductal adenocarcinoma with mismatch repair deficiency resected after long-term observation. Clin J Gastroenterol 13, 959–968 (2020). https://doi.org/10.1007/s12328-020-01128-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12328-020-01128-1

Keywords

Search

Navigation