Skip to main content
SpringerLink
Log in

Imaging and staging of neuroendocrine cervical cancer

  • Pictorial essay
  • Published:
Abdominal Radiology Aims and scope Submit manuscript

Abstract

Neuroendocrine cervical cancer (NECC) is a rare and aggressive subtype of cervical cancer, accounting for less than 2% of cervical tumors. They are divided into low-grade and high-grade tumors. High-grade NECC is associated with human papillomavirus (HPV) 18 and to a smaller extent type 16. The most common molecular alterations in NECC include PIK3CA, KRAS, and TP53 mutations. Immunohistochemical staining for CD56, synaptophysin, and chromogranin is a helpful tool in the diagnosis. NECCs pose a significant clinical and therapeutic challenge because of their aggressive nature which is explained by their tendency towards early nodal and hematogenous spread. They have a median survival of 21–22 months, compared to 10 years in cervical squamous cell carcinomas. NECCs have a homogeneous high T2 signal intensity, homogeneous contrast enhancement and lower ADC values in MRI, compared to non-neuroendocrine tumors of the cervix. It is recommended to treat NECC with a multimodality therapeutic approach combining radical hysterectomy, systemic chemotherapy, and radiotherapy. The objective of this manuscript is to address the pathogenesis of NECC, elaborate the role of radiological imaging in the diagnosis and staging of NECCs, evaluate their prognosis, and summarize the suggested management plans for this lethal disease.

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

Modified from Gardner et al. [38]

Similar content being viewed by others

References

  1. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S (2010) The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 39(6):707–712. https://doi.org/10.1097/MPA.0b013e3181ec124e

    Article  Google Scholar 

  2. Gadducci A, Carinelli S, Aletti G (2017) Neuroendrocrine tumors of the uterine cervix: a therapeutic challenge for gynecologic oncologists. Gynecol Oncol 144(3):637–646. https://doi.org/10.1016/j.ygyno.2016.12.003

    Article  PubMed  Google Scholar 

  3. Howitt BE, Kelly P, McCluggage WG (2017) Pathology of neuroendocrine tumours of the female genital tract. Curr Oncol Rep 19(9):59. https://doi.org/10.1007/s11912-017-0617-2

    Article  PubMed  Google Scholar 

  4. Burzawa J, Gonzales N, Frumovitz M (2015) Challenges in the diagnosis and management of cervical neuroendocrine carcinoma. Expert Rev Anticancer Ther 15(7):805–810. https://doi.org/10.1586/14737140.2015.1047767

    Article  CAS  PubMed  Google Scholar 

  5. Colgan TJ, Hirschowitz L, Kim I, McCluggage WG (2014) Tumors of the uterine cervix: neuroendocrine tumors. In: Kurman RJ, Carcangiu ML, Herrington CS, Young RH (eds) WHO classification of tumours of female reproductive organs, 4th edn. Lyon: IARC

    Google Scholar 

  6. Toki T, Katayama Y, Motoyama T (1996) Small-cell neuroendocrine carcinoma of the uterine cervix associated with micro-invasive squamous cell carcinoma and adenocarcinoma in situ. Pathol Int 46(7):520–525. https://doi.org/10.1111/j.1440-1827.1996.tb03648.x

    Article  CAS  PubMed  Google Scholar 

  7. Ganesan R, Hirschowitz L, Dawson P, et al. (2016) Neuroendocrine carcinoma of the cervix: review of a series of cases and correlation with outcome. Int J Surg Pathol 24(6):490–496. https://doi.org/10.1177/1066896916643385

    Article  CAS  Google Scholar 

  8. Duan X, Ban X, Zhang X, et al. (2016) MR imaging features and staging of neuroendocrine carcinomas of the uterine cervix with pathological correlations. Eur Radiol 26(12):4293–4302. https://doi.org/10.1007/s00330-016-4327-1

    Article  PubMed  Google Scholar 

  9. Cohen JG, Kapp DS, Shin JY, et al. (2010) Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients. Am J Obstet Gynecol 203(4):341.e1–346.e6. https://doi.org/10.1016/j.ajog.2010.04.019

    Article  Google Scholar 

  10. Boruta DM 2nd, Schorge JO, Duska LA, et al. (2001) Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine cervix. Gynecol Oncol 81(1):82–87. https://doi.org/10.1006/gyno.2000.6118

    Article  PubMed  Google Scholar 

  11. Chan JK, Tsui WM, Tung SY, Ching RC (1989) Endocrine cell hyperplasia of the uterine cervix. A precursor of neuroendocrine carcinoma of the cervix? Am J Clin Pathol 92(6):825–830

    Article  CAS  Google Scholar 

  12. Eichhorn JH, Young RH (2001) Neuroendocrine tumors of the genital tract. Am J Clin Pathol 115(Suppl 1):S94–S112. https://doi.org/10.1309/64cw-wkgk-49ef-byd1

    Article  PubMed  Google Scholar 

  13. Castle PE, Pierz A, Stoler MH (2018) 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. https://doi.org/10.1016/j.ygyno.2017.12.001

    Article  PubMed  Google Scholar 

  14. Stoler MH, Mills SE, Gersell DJ, Walker AN (1991) Small-cell neuroendocrine carcinoma of the cervix. A human papillomavirus type 18-associated cancer. Am J Surg Pathol 15(1):28–32. https://doi.org/10.1097/00000478-199101000-00003

    Article  CAS  PubMed  Google Scholar 

  15. Wistuba II, Thomas B, Behrens C, et al. (1999) Molecular abnormalities associated with endocrine tumors of the uterine cervix. Gynecol Oncol 72(1):3–9. https://doi.org/10.1006/gyno.1998.5248

    Article  CAS  PubMed  Google Scholar 

  16. Frumovitz M, Burzawa JK, Byers LA, et al. (2016) Sequencing of mutational hotspots in cancer-related genes in small cell neuroendocrine cervical cancer. Gynecol Oncol 141(3):588–591. https://doi.org/10.1016/j.ygyno.2016.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Atienza-Amores M, Guerini-Rocco E, Soslow RA, Park KJ, Weigelt B (2014) Small cell carcinoma of the gynecologic tract: a multifaceted spectrum of lesions. Gynecol Oncol 134(2):410–418. https://doi.org/10.1016/j.ygyno.2014.05.017

    Article  PubMed  Google Scholar 

  18. McCluggage WG, Kennedy K, Busam KJ (2010) An immunohistochemical study of cervical neuroendocrine carcinomas: neoplasms that are commonly TTF1 positive and which may express CK20 and P63. Am J Surg Pathol 34(4):525–532. https://doi.org/10.1097/PAS.0b013e3181d1d457

    Article  PubMed  Google Scholar 

  19. Brierley JD, Gospodarowicz MK, Wittekind C (eds) (2017) TNM Classification of Malignant Tumours, 8th edn. Chichester: Wiley

    Google Scholar 

  20. McCusker ME, Cote TR, Clegg LX, Tavassoli FJ (2003) Endocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma. Gynecol Oncol 88(3):333–339. https://doi.org/10.1016/S0090-8258(02)00150-6

    Article  PubMed  Google Scholar 

  21. Li JD, Zhuang Y, Li YF, et al. (2011) A clinicopathological aspect of primary small-cell carcinoma of the uterine cervix: a single-centre study of 25 cases. J Clin Pathol 64(12):1102–1107. https://doi.org/10.1136/jclinpath-2011-200274

    Article  PubMed  Google Scholar 

  22. Kuji S, Hirashima Y, Nakayama H, et al. (2013) Diagnosis, clinicopathologic features, treatment, and prognosis of small cell carcinoma of the uterine cervix; Kansai Clinical Oncology Group/Intergroup study in Japan. Gynecol Oncol 129(3):522–527. https://doi.org/10.1016/j.ygyno.2013.02.025

    Article  PubMed  Google Scholar 

  23. Wang KL, Yang YC, Wang TY, et al. (2006) Neuroendocrine carcinoma of the uterine cervix: a clinicopathologic retrospective study of 31 cases with prognostic implications. J Chemother 18(2):209–216. https://doi.org/10.1179/joc.2006.18.2.209

    Article  PubMed  Google Scholar 

  24. Nagao S, Miwa M, Maeda N, et al. (2015) Clinical features of neuroendocrine carcinoma of the uterine cervix: a single-institution retrospective review. Int J Gynecol Cancer 25(7):1300–1305. https://doi.org/10.1097/IGC.0000000000000495

    Article  PubMed  Google Scholar 

  25. Chen J, Macdonald OK, Gaffney DK (2008) Incidence, mortality, and prognostic factors of small cell carcinoma of the cervix. Obstet Gynecol 111(6):1394–1402. https://doi.org/10.1097/AOG.0b013e318173570b

    Article  PubMed  Google Scholar 

  26. Viswanathan AN, Deavers MT, Jhingran A, et al. (2004) Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence. Gynecol Oncol 93(1):27–33. https://doi.org/10.1016/j.ygyno.2003.12.027

    Article  CAS  PubMed  Google Scholar 

  27. Lin Y, Lin WY, Liang JA, et al. (2012) Opportunities for 2-[(18)F] fluoro-2-deoxy-d-glucose PET/CT in cervical–vaginal neuroendocrine carcinoma: case series and literature review. Korean J Radiol 13(6):760–770. https://doi.org/10.3348/kjr.2012.13.6.760

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bonardel G, Chargari C, Gontier E, et al. (2009) Positron emission tomography in the management of cervix cancer patients. Cancer Radiother 13(6–7):490–498. https://doi.org/10.1016/j.canrad.2009.06.016

    Article  CAS  PubMed  Google Scholar 

  29. Kaur H, Verschraegen CF (2012) Cervical cancer. Oncologic imaging: a multidisciplinary approach. W.B. Saunders, Philadelphia, pp 441–453. https://doi.org/10.1016/b978-1-4377-2232-1.00025-5

    Chapter  Google Scholar 

  30. Dappa E, Elger T, Hasenburg A, et al. (2017) The value of advanced MRI techniques in the assessment of cervical cancer: a review. Insights Imaging 8(5):471–481. https://doi.org/10.1007/s13244-017-0567-0

    Article  PubMed  PubMed Central  Google Scholar 

  31. Damian A, Lago G, Rossi S, Alonso O, Engler H (2017) Early detection of bone metastasis in small cell neuroendocrine carcinoma of the cervix by 68Ga-DOTATATE PET/CT imaging. Clin Nucl Med 42(3):216–217. https://doi.org/10.1097/RLU.0000000000001498

    Article  PubMed  Google Scholar 

  32. Yang J, Kan Y, Ge BH, et al. (2014) Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. Acta Radiol 55(4):389–398. https://doi.org/10.1177/0284185113496679

    Article  PubMed  Google Scholar 

  33. Salvo G, Ramirez PT, Levenback CF, et al. (2017) Sensitivity and negative predictive value for sentinel lymph node biopsy in women with early-stage cervical cancer. Gynecol Oncol 145(1):96–101. https://doi.org/10.1016/j.ygyno.2017.02.005

    Article  PubMed  PubMed Central  Google Scholar 

  34. Fields EC, Weiss E (2016) A practical review of magnetic resonance imaging for the evaluation and management of cervical cancer. Radiat Oncol 11(1):15. https://doi.org/10.1186/s13014-016-0591-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sala E, Wakely S, Senior E, Lomas D (2007) MRI of malignant neoplasms of the uterine corpus and cervix. AJR 188(6):1577–1587. https://doi.org/10.2214/AJR.06.1196

    Article  PubMed  Google Scholar 

  36. Frumovitz M, Munsell MF, Burzawa JK, et al. (2017) Combination therapy with topotecan, paclitaxel, and bevacizumab improves progression-free survival in recurrent small cell neuroendocrine carcinoma of the cervix. Gynecol Oncol 144(1):46–50. https://doi.org/10.1016/j.ygyno.2016.10.040

    Article  CAS  PubMed  Google Scholar 

  37. Satoh T, Takei Y, Treilleux I, et al. (2014) Gynecologic Cancer InterGroup (GCIG) consensus review for small cell carcinoma of the cervix. Int J Gynecol Cancer 24(9 Suppl 3):S102–S108. https://doi.org/10.1097/IGC.0000000000000262

    Article  PubMed  Google Scholar 

  38. Gardner GJ, Reidy-Lagunes D, Gehrig PA (2011) Neuroendocrine tumors of the gynecologic tract: a Society of Gynecologic Oncology (SGO) clinical document. Gynecol Oncol 122(1):190–198. https://doi.org/10.1016/j.ygyno.2011.04.011

    Article  PubMed  Google Scholar 

  39. Stecklein SR, Jhingran A, Burzawa J, et al. (2016) Patterns of recurrence and survival in neuroendocrine cervical cancer. Gynecol Oncol 143(3):552–557. https://doi.org/10.1016/j.ygyno.2016.09.011

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lee JM, Lee KB, Nam JH, et al. (2008) Prognostic factors in FIGO stage IB-IIA small cell neuroendocrine carcinoma of the uterine cervix treated surgically: results of a multi-center retrospective Korean study. Ann Oncol 19(2):321–326. https://doi.org/10.1093/annonc/mdm465

    Article  PubMed  Google Scholar 

  41. Singh S, Redline R, Resnick KE (2015) Fertility-sparing management of a stage IB1 small cell neuroendocrine cervical carcinoma with radical abdominal trachelectomy and adjuvant chemotherapy. Gynecol Oncol Rep 13:5–7. https://doi.org/10.1016/j.gore.2015.04.004

    Article  PubMed  PubMed Central  Google Scholar 

  42. Hertel H, Kohler C, Grund D, et al. (2006) Radical vaginal trachelectomy (RVT) combined with laparoscopic pelvic lymphadenectomy: prospective multicenter study of 100 patients with early cervical cancer. Gynecol Oncol 103(2):506–511. https://doi.org/10.1016/j.ygyno.2006.03.040

    Article  PubMed  Google Scholar 

  43. Dongol S, Tai Y, Shao Y, Jiang J, Kong B (2014) A retrospective clinicopathological analysis of small-cell carcinoma of the uterine cervix. Mol Clin Oncol 2(1):71–75. https://doi.org/10.3892/mco.2013.193

    Article  PubMed  Google Scholar 

  44. Elit L, Fyles AW, Oliver TK, et al. (2010) Follow-up for women after treatment for cervical cancer. Curr Oncol 17(3):65–69. https://doi.org/10.3747/co.v17i3.514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

We thank Kelly Kage, medical illustrator at MD Anderson Cancer Center for the illustrations provided in this article.

Author information

Authors and Affiliations

  1. Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Sherif Elsherif, Erika G. L. C. Odisio, Silvana Faria, Sanaz Javadi, Sireesha Yedururi & Priya Bhosale

  2. Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Michael Frumovitz

  3. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Preetha Ramalingam

Authors
  1. Sherif Elsherif
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erika G. L. C. Odisio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvana Faria
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sanaz Javadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sireesha Yedururi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael Frumovitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Preetha Ramalingam
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Priya Bhosale
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sherif Elsherif.

Ethics declarations

Conflict of interest

The authors declare that they have no disclosure or conflict of interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elsherif, S., Odisio, E.G.L.C., Faria, S. et al. Imaging and staging of neuroendocrine cervical cancer. Abdom Radiol 43, 3468–3478 (2018). https://doi.org/10.1007/s00261-018-1667-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00261-018-1667-0

Keywords

Search

Navigation