Skip to main content

Advertisement

SpringerLink
Log in

Clinicopathologic features and lymph node metastasis pattern of the cervical MiNEN

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare type of cervical tumor. Its clinicopathological features, lymph node (LN) metastatic patterns and outcomes are still unclear.

Methods

We have analyzed the clinicopathological information of 26 patients with cervical MiNEN.

Results

The median age of onset for cervical MiNEN was 48 years. Macroscopically, polyps and nodules were the main types. The neuroendocrine components included small cell neuroendocrine carcinoma (SCNEC) (14/26 cases), large cell neuroendocrine carcinoma (LCNEC) (10/26 cases), and typical carcinoid (2/26 cases). Non-neuroendocrine components included adenocarcinoma (AC) (12/26, including one case of AC in situ) and squamous cell carcinoma (SC) (10/26) and adeno-squamous cell carcinoma (ASC) (4/26). Of the 16 AC cases, 15 were human papilloma virus (HPV)-associated AC and one was HPV-independent AC. Except for the case of MiNEN with HPV-independent AC, all cases were diffusely and strongly positive for p16 protein. The lympho-vascular space invasion (LVSI) was seen in 17/26 cases, and the components that invade lymphatic vessels were mainly neuroendocrine carcinomas (NECs) (15/17), followed by SC (1/17) and AC (1/17). Ten patients developed LN metastases, including six in combined SCNECs (6/14) and four in combined LCNECs (4/10); the metastatic component was pure NEC in eight cases (8/10) and SC or AC in two cases (2/10).

Conclusions

NEC component is the key factor that determines the clinical behavior and prognosis of cervical MiNEN.

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

Similar content being viewed by others

References

  1. G. Rindi, D.S. Klimstra, B. Abedi-Ardekani et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod. Pathol. 31(12), 1770–1786 (2018)

    Article  Google Scholar 

  2. E. Guadagno, G. De Rosa, M. Del Basso De Caro, Neuroendocrine tumours in rare sites: differences in nomenclature and diagnostics-a rare and ubiquitous histotype. J. Clin. Pathol. 69(7), 563–574 (2016)

    Article  CAS  Google Scholar 

  3. B. Margolis, A.I. Tergas, L. Chen et al. Natural history and outcome of neuroendocrine carcinoma of the cervix. Gynecol. Oncol. 141(2), 247–254 (2016)

    Article  Google Scholar 

  4. P. Sitthinamsuwan, N. Angkathunyakul, T. Chuangsuwanich, P. Inthasorn, Neuroendocrine carcinomas of the uterine cervix: a clinicopathological study. J. Med. Assoc. Thai. 96(1), 83–90 (2013)

    PubMed  Google Scholar 

  5. B.E. Howitt, P. Kelly, W.G. McCluggage, Pathology of neuroendocrine tumours of the female genital tract. Curr. Oncol. Rep. 19(9), 59 (2017)

    Article  Google Scholar 

  6. C.B. Tempfer, I. Tischoff, A. Dogan et al. Neuroendocrine carcinoma of the cervix: a systematic review of the literature. BMC Cancer 18(1), 530 (2018)

    Article  Google Scholar 

  7. R.E. Emerson, H. Michael, M. Wang, S. Zhang, L.M. Roth, L. Cheng, Cervical carcinomas with neuroendocrine differentiation: a report of 28 cases with immunohistochemical analysis and molecular genetic evidence of common clonal origin with coexisting squamous and adenocarcinomas. Int. J. GynecolPathol. 35(4), 372–384 (2016)

    CAS  Google Scholar 

  8. A. Gadducci, S. Carinelli, G. Aletti, Neuroendrocrine tumors of the uterine cervix: A therapeutic challenge for gynecologic oncologists. Gynecol. Oncol. 144(3), 637–646 (2017)

    Article  Google Scholar 

  9. A. Bermúdez, S. Vighi, A. García, J. Sardi, Neuroendocrine cervical carcinoma: a diagnostic and therapeutic challenge. Gynecol. Oncol. 82(1), 32–39 (2001)

    Article  Google Scholar 

  10. E. Fadiloglu, A. Karalok, O. Turkmen et al. Amphricrine carcinoma of the cervix-adenoneuroendocrine tumor: a case report. Turk. J. Obstet. Gynecol. 13(2), 99–102 (2016)

    Article  Google Scholar 

  11. H. Hara, E. Ishii, T. Hondo, M. Nakagawa, K. Teramoto, T. Oyama, Cytological features of atypical carcinoid combined with adenocarcinoma of the uterine cervix. Diagn. Cytopathol. 40(8), 724–728 (2012)

    Article  Google Scholar 

  12. C. Nishimura, H. Naoe, S. Hashigo et al. Pancreatic metastasis from mixed adenoneuroendocrine carcinoma of the uterine cervix: a case report. Case Rep. Oncol. 6(2), 256–262 (2013)

    Article  Google Scholar 

  13. P. Ramalingam, A. Malpica, M.T. Deavers, Mixed endocervical adenocarcinoma and high-grade neuroendocrine carcinoma of the cervix with ovarian metastasis of the former component: a report of 2 cases. Int. J. Gynecol. Pathol. 31(5), 490–496 (2012)

    Article  Google Scholar 

  14. L.C. Horn, B. Hentschel, K. Bilek, C.E. Richter, J. Einenkel, C. Leo, Mixed small cell carcinomas of the uterine cervix: prognostic impact of focal neuroendocrine differentiation but not of Ki-67 labeling index. Ann. Diagn. Pathol. 10(3), 140–143 (2006)

    Article  Google Scholar 

  15. S.I. Lee, M. Atri, 2018 FIGO staging system for uterine cervical cancer: enter cross-sectional imaging. Radiology 292(1), 15–24 (2019)

    Article  Google Scholar 

  16. K. Sodsanrat, N. Saeaib, T. Liabsuetrakul, Comparison of clinical manifestations and survival outcomes between neuroendocrine tumor and squamous cell carcinoma of the uterine cervix: Results from a tertiary center in southern Thailand. J. Med. Assoc. Thai. 98(8), 725–733 (2015)

    PubMed  Google Scholar 

  17. K.L. Wang, Y.C. Yang, T.Y. Wang et al. Neuroendocrine carcinoma of the uterine cervix: a clinicopathologic retrospective study of 31 cases with prognostic implications. J. Chemother. 18(2), 209–216 (2006)

    Article  Google Scholar 

  18. P.E. Castle, A. Pierz, M.H. Stoler, A systematic review and meta-analysis on the attribution of human papillomavirus (HPV) in neuroendocrine cancers of the cervix. Gynecol. Oncol. 148(2), 422–429 (2018)

    Article  Google Scholar 

  19. W. Small Jr, M.A. Bacon, A. Bajaj et al. Cervicalcancer: a global health crisis. Cancer 123(13), 2404–2412 (2017)

    Article  Google Scholar 

  20. K. Holl, A.M. Nowakowski, N. Powell et al. Human papillomavirus prevalence and type-distribution in cervical glandular neoplasias: results from a European multinational epidemiological study. Int. J. Cancer 137(12), 2858–2868 (2015)

    Article  CAS  Google Scholar 

  21. N. Missaoui, S. Mestiri, A. Bdioui et al. HPV infection and p16INK4A and TP53 expression in rare cancers of the uterine cervix. Pathol. Res. Pr. 214(4), 498–506 (2018)

    Article  CAS  Google Scholar 

  22. L.C. Horn, K. Lindner, G. Szepankiewicz et al. p16, p14, p53, and cyclin D1 expression and HPV analysis in small cell carcinomas of the uterine cervix. Int. J. Gynecol. Pathol. 25(2), 182–186 (2006)

    Article  Google Scholar 

  23. G. Salvo, A. Gonzalez Martin, N.R. Gonzales, M. Frumovitz, Updates and management algorithm for neuroendocrine tumors of the uterine cervix. Int. J. Gynecol. Cancer 29(6), 986–995 (2019)

    Article  Google Scholar 

  24. M.S. Cavalcanti, A.M. Schultheis, C. Ho et al. Mixed mesonephric adenocarcinoma and high-grade neuroendocrine carcinoma of the uterine cervix. Int. J. Gynecol. Pathol. 36(1), 76–89 (2017)

    Article  Google Scholar 

  25. Y. Mikami, W.G. McCluggage, Endocervical glandular lesions exhibiting gastric differentiation: an emerging spectrum of benign, premalignant, and malignant lesions. Adv. Anat. Pathol. 20(4), 227–237 (2013)

    Article  CAS  Google Scholar 

  26. Y. Xue, B. San Luis, D.P. Lane, Intratumour heterogeneity of p53 expression; causes and consequences. J. Pathol. 249(3), 274–285 (2019)

    Article  CAS  Google Scholar 

  27. S. Muraoka, T. Takahashi, M. Ando, Y. Nishikawa, M. Fujita, A. Shimoda, Minute carcinoid tumor of the uterine cervix associated with microinvasive adenocarcinoma, with reference to its histogenesis. Acta Pathol. Jpn. 37(7), 1183–1198 (1987)

    CAS  PubMed  Google Scholar 

  28. P. Gaur, E.L. Sceusi, S. Samuel et al. Identification of cancer stem cells in human gastrointestinal carcinoid and neuroendocrine tumors. Gastroenterology 141(5), 1728–1737 (2011)

    Article  CAS  Google Scholar 

  29. K. Sukpan, J. Settakorn, S. Khunamornpong, C. Cheewakriangkrai, J. Srisomboon, S. Siriaunkgul, Expression of survivin, CD117, and C-erbB-2 in neuroendocrine carcinoma of the uterine cervix. Int. J. Gynecol. Cancer 21(5), 911–917 (2011)

    Article  Google Scholar 

  30. E.E. Sheets, M.L. Berman, C.K. Hrountas, S.Y. Liao, P.J. DiSaia, Surgically treated, early-stage neuroendocrine small-cell cervical carcinoma. Obstet. Gynecol. 71(1), 10–14 (1988)

    CAS  PubMed  Google Scholar 

  31. V.M. Abeler, R. Holm, J.M. Nesland, K.E. Kjørstad, Small cell carcinoma of the cervix. A clinicopathologic study of 26 patients. Cancer 73(3), 672–677 (1994)

    Article  CAS  Google Scholar 

  32. I. Păun, G. Becheanu, A.I. Costin et al. Aspects regarding nomenclature, classification and pathology of neuroendocrine neoplasms of the digestive system-a review. Rom. J. Morphol. Embryol. 59(3), 673–678 (2018)

    PubMed  Google Scholar 

  33. S. La Rosa, A. Marando, F. Sessa, C. Capella, Mixed adenoneuroendocrine carcinomas (MANECs) of the gastrointestinal tract: an update. Cancers 4(1), 11–30 (2012)

    Article  Google Scholar 

  34. A.N. Viswanathan, M.T. Deavers, A. Jhingran, P.T. Ramirez, C. Levenback, P.J. Eifel, Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence. Gynecol. Oncol. 93(1), 27–33 (2004)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank the Natural Science Foundation of Liaoning Province, Shenyang High-level Innovative Talents Program and Liaoning Cancer Hospital and Institute, Dalian University of Technology “Medical-industrial interdisciplinary research fund” for their financial supports. We also will thank BioMed Proofreading® LLC for English language editing.

Funding

This work was supported by grants from the Natural Science Foundation of Liaoning Province (2020-ZLLH-45), Shenyang High-level Innovative Talents Program (RC190447) and Liaoning Cancer Hospital and Institute, Dalian University of Technology “Medical-industrial interdisciplinary research fund” (LD202021).

Author information

Authors and Affiliations

  1. Department of Pathology, Fourth Affiliated Hospital of China Medical University, Shenyang, China

    Huihui Xu

  2. Department of Pathology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China

    Zehua Zhao & Yanmei Zhu

Authors
  1. Huihui Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zehua Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yanmei Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.X. contributed to the scripting of this manuscript. Z.Z. contributed to the immunohistochemical staining, searching for clinical data and obtaining prognostic information. Y.Z. contributed to the overall design and revision of this manuscript.

Corresponding author

Correspondence to Yanmei Zhu.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Liaoning Cancer Hospital and Institute (Ethics Committee Approval Document: 20200815YG, 2020.8.19- 2021.8.18).

Additional information

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, H., Zhao, Z. & Zhu, Y. Clinicopathologic features and lymph node metastasis pattern of the cervical MiNEN. Endocrine 76, 474–483 (2022). https://doi.org/10.1007/s12020-022-02992-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-022-02992-2

Keywords

Search

Navigation