Cervical Neuroendocrine Tumours, Mixed Epithelial/Mesenchymal and Mesenchymal Tumours and Other Miscellaneous Lesions

  • Anthony T. Williams
  • Raji GanesanEmail author


Cervical cancers are the third most common cancers of the female genital tract. Most of these neoplasms are human papillomavirus (HPV)-related squamous cell carcinomas and adenocarcinomas, but in addition a wide range of uncommon and rare tumours may occur. These may present particular diagnostic challenges resulting from their rarity and the differential diagnoses which may arise at this site.

Neuroendocrine carcinomas (NEC) are not uncommonly encountered in routine practice. They are aetiologically related to HPV and may be associated with squamous and adenocarcinoma or their precursors. Diagnosis of NEC is important as it has a poorer outcome and is treated aggressively with non-surgical modalities. Mixed tumours include the common cervical polyps and the rarer adenosarcomas. The latter has a potential for recurrence and sarcomatous overgrowth. Of the cervical sarcomas, embryonal rhabdomyosarcoma is the commonest at this site and has distinctive appearance and clinical profile.

In general, accurate diagnosis of these entities is important in determining optimal patient management since some tumours may be associated with tumour syndromes and extracervical disease.


Neuroendocrine carcinoma Sarcoma Mixed tumour Adenosarcoma Rhabdomyosarcoma Immunohisto chemistry Classification 


  1. 1.
    Crowder S, Tuller E. Small cell carcinoma of the female genital tract. Semin Oncol. 2007;34:57–63.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO classification of tumours of the female reproductive organs. 4th ed. Lyon: IARC; 2014.Google Scholar
  3. 3.
    Horn LC, Hentschel B, Bilek K, et al. Mixed small cell carcinomas of the uterine cervix: prognostic impact of focal neuroendocrine differentiation but not of Ki-67 labeling index. Ann Diagn Pathol. 2006;10:140–3.CrossRefGoogle Scholar
  4. 4.
    Modlin IM, Shapiro MD, Kidd M. An analysis of rare carcinoid tumors: clarifying these clinical conundrums. World J Surg. 2005;29:92–101.CrossRefGoogle Scholar
  5. 5.
    Papatsimpas G, Samaras I, Theodosiou P, Papacharalampous K, Maragkouli E, Papadopoulos NV, Tsapakidis K, Litos I, Sogka E, Kostopoulou E, Koukoulis GK. A case of cervical carcinoid and review of the literature. Case Rep Oncol. 2017;10(2):737–42.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Rekhi B, Patil B, Deodhar KK, et al. Spectrum of neuroendocrine carcinomas of the uterine cervix, including histopathologic features, terminology, immunohistochemical profile, and clinical outcomes in a series of 50 cases from a single institution in India. Ann Diagn Pathol. 2013;17:1–9.CrossRefGoogle Scholar
  7. 7.
    Kim JY, Hong SM, Ro JY. Recent updates on grading and classification of neuroendocrine tumors. Ann Diagn Pathol. 2017;29:11–6.CrossRefGoogle Scholar
  8. 8.
    McCluggage WG, Kennedy K, Busam KJ. An immunohistochemical study of cervical neuroendocrine carcinomas: Neoplasms that are commonly TTF1 positive and which may express CK20 and P63. Am J Surg Pathol. 2010;34:525–32.CrossRefGoogle Scholar
  9. 9.
    Liau JY, Tsai JH, Jeng YM, et al. The diagnostic utility of PAX8 for neuroendocrine tumors: An immunohistochemical reappraisal. Appl Immunohistochem Mol Morphol. 2016;24:57–63.CrossRefGoogle Scholar
  10. 10.
    Atienza-Amores M, Guerini-Rocco E, Soslow RA, et al. Small cell carcinoma of the gynecologic tract: a multifaceted spectrum of lesions. Gynecol Oncol. 2014;134:410–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Hartley CP, Steinmetz HB, Memoli VA, Tafe LJ. Small cell neuroendocrine carcinomas of the lung do not harbor high-risk human papillomavirus. Hum Pathol. 2015;46:577–82.CrossRefPubMedGoogle Scholar
  12. 12.
    Wistuba II, Thomas B, Behrens C, Onuki N, et al. Molecular abnormalities associated with endocrine tumors of the uterine cervix. Gynecol Oncol. 1999;72:3–9.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Emerson RE, Michael H, Wang M. 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 Gynecol Pathol. 2016;35:372–84.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Ganesan R, Hirschowitz L, Dawson P, et al. Neuroendocrine carcinoma of the cervix: Review of a series of cases and correlation with outcome. Int J Surg Pathol. 2016;24:490–6.CrossRefGoogle Scholar
  15. 15.
    Gardner GJ, Reidy-Lagunes D, Gehrig PA. Neuroendocrine tumors of the gynecologic tract: A Society of Gynecologic Oncology (SGO) clinical document. Gynecol Oncol. 2011;122:190–8.CrossRefGoogle Scholar
  16. 16.
    Margolis B, Tergas AI, Chen L, et al. Natural history and outcome of neuroendocrine carcinoma of the cervix. Gynecol Oncol. 2016;141:247–54.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Intaraphet S, Kasatpibal N, Siriaunkgul S, et al. Prognostic factors for small cell neuroendocrine carcinoma of the uterine cervix: an institutional experience. Int J Gynecol Cancer. 2014;24:272–9.CrossRefGoogle Scholar
  18. 18.
    Tirlapur SA, Adeyemo A, O'Gorman N, et al. Clinico-pathological study of cervical polyps. Arch Gynecol Obstet. 2010;282:535–8.CrossRefGoogle Scholar
  19. 19.
    McQuillan SK, Grover SR, Pyman J, et al. Literature review of benign Müllerian papilloma contrasted with vaginal rhabdomyosarcoma. J Pediatr Adolesc Gynecol. 2016;29:333–7.CrossRefGoogle Scholar
  20. 20.
    Bucella D, Frédéric B, Noël JC. Giant cervical polyp: a case report and review of a rare entity. Arch Gynecol Obstet. 2008;278:295–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Godfrey GJ, Moore G, Alatassi H. Presentation of renal cell carcinoma as cervical polyp metastasis. J Low Genit Tract Dis. 2010;14:387–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Levy RA, Kumarapeli AR, Spencer HJ, Quick CM. Cervical polyps: is histologic evaluation necessary? Pathol Res Pract. 2016;212:800–3.CrossRefPubMedGoogle Scholar
  23. 23.
    Gilks CB, Young RH, Clement PB, et al. Adenomyomas of the uterine cervix of of endocervical type: a report of ten cases of a benign cervical tumor that may be confused with adenoma malignum. Mod Pathol. 1996;9:220–4.PubMedGoogle Scholar
  24. 24.
    Casey S, McCluggage WG. Adenomyomas of the uterine cervix: report of a cohort including endocervical and novel variants. Histopathology. 2015;66:420–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Rabban JT, McAlhany S, Lerwill MF, Grenert JP, Zaloudek CJ. PAX2 distinguishes benign mesonephric and mullerian glandular lesions of the cervix from endocervical adenocarcinoma, including minimal deviation adenocarcinoma. Am J Surg Pathol. 2010;34:137–46.CrossRefGoogle Scholar
  26. 26.
    Bachurska S, Yamakov K, Belovezdov V, et al. Case of atypical polypoid adenomyoma of the uterine cervix. Akush Ginekol (Sofiia). 2013;52:67–70.Google Scholar
  27. 27.
    McCluggage WG. Mullerian adenosarcoma of the female genital tract. Adv Anat Pathol. 2010;17:122–9.CrossRefGoogle Scholar
  28. 28.
    Comunoğlu N, Comunoğlu C, Başsüllü N, et al. Müllerian adenosarcoma with sarcomatous overgrowth of the cervix: unusual large polypoid mass. Ups J Med Sci. 2007;112:67–72.CrossRefPubMedGoogle Scholar
  29. 29.
    Gallardo A, Prat J. Mullerian adenosarcoma: a clinicopathologic and immunohistochemical study of 55 cases challenging the existence of adenofibroma. Am J Surg Pathol. 2009;33:278–88.CrossRefPubMedGoogle Scholar
  30. 30.
    Verschraegen CF, Vasuratna A, Edwards C, et al. Clinicopathologic analysis of mullerian adenosarcoma: the M.D. Anderson Cancer Center experience. Oncol Rep. 1998;5:939–44.Google Scholar
  31. 31.
    Kim M, Lee C, Choi H, et al. Carcinosarcoma of the uterine cervix arising from Müllerian ducts. Obstet Gynecol Sci. 2015;58:251–5.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Meguro S, Yasuda M, Shimizu M, et al. Mesonephric adenocarcinoma with a sarcomatous component, a notable subtype of cervical carcinosarcoma: a case report and review of the literature. Diagn Pathol. 2013;8:74.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Grayson W, Taylor LF, Cooper K. Carcinosarcoma of the uterine cervix: a report of eight cases with immunohistochemical analysis and evaluation of human papillomavirus status. Am J Surg Pathol. 2001;25:338–47.CrossRefGoogle Scholar
  34. 34.
    Roma AA. Mesonephric carcinosarcoma involving uterine cervix and vagina: report of 2 cases with immunohistochemical positivity for PAX2, PAX8, and GATA-3. Int J Gynecol Pathol. 2014;33:624–9.CrossRefGoogle Scholar
  35. 35.
    Fadare O. Uncommon sarcomas of the uterine cervix: a review of selected entities. Diagn Pathol. 2006;1:30.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Clement PB. Miscellaneous primary tumors and metastatic tumours of the uterine cervix. Semi Diagn Pathol. 1990;7:228–48.Google Scholar
  37. 37.
    Bansal S, Lewin SN, Burke WM, et al. Sarcoma of the cervix: natural history and outcomes. Gynecol Oncol. 2010;118:134–8.CrossRefGoogle Scholar
  38. 38.
    Khosla D, Gupta R, Srinivasan R, et al. Sarcomas of Uterine cervix. Int J Gynecol Cancer. 2012;22:1026–30.CrossRefGoogle Scholar
  39. 39.
    Daya D, Scully RE. Sarcoma botyroides of the uterine cervix in young women: a clinicopathological analysis of 13 cases. Gynecol Oncol. 1998;29:290–304.CrossRefGoogle Scholar
  40. 40.
    Dehner LP, Jarzebowski JA, Hill DA. Embryonal rhabdomyosarcoma of the uterine cervix: a report of 14 cases and a discussion of its unusual clinicopathological associations. Mod Pathol. 2012;25:602–14.CrossRefGoogle Scholar
  41. 41.
    Krissemen ML, Wang WL, Sullinger J, et al. Rhabdomyosarcoma of the cervix in adult women and younger patients. Gynecol Oncol. 2012;126:351–639.CrossRefGoogle Scholar
  42. 42.
    Li FL, Gupta M, McCluggage WG, et al. Embryonal rhabdomyosarcoma (botyroid type) of the uterine corpus and cervix in adult women. Am J Surg Pathol. 2013;37:344–55.CrossRefGoogle Scholar
  43. 43.
    Boardman CH, Webb MJ, Jefferies JA. Low-grade endometrial stromal sarcoma of the ectocervix after therapy for breast cancer. Gynecol Oncol. 2006;79:120–3.CrossRefGoogle Scholar
  44. 44.
    McCluggage WG, Ganesan R, Herrington CS. Endometrial stromal sarcomas with extensive endometrioid glandular differentiation: report of a series with emphasis on the potential for misdiagnosis and discussion of the differential diagnosis. Histopathology. 2009;54:365–73.CrossRefGoogle Scholar
  45. 45.
    Cernelc J, Volchek M. YWHAE-FAM22 high grade endometrial stromal sarcoma presenting as a cervical mass. Pathology. 2017;49(s1):S68.CrossRefGoogle Scholar
  46. 46.
    Nielsen GP, Oliva E, Young RH, et al. Alveolar soft part sarcoma of the female genital tract: a report of nine cases and review of the literature. Int J Gynecol Pathol. 1995;14:283–92.CrossRefGoogle Scholar
  47. 47.
    Feng M, Jian W, He Y, et al. Primary alveolar soft part sarcoma of the uterine cervix. A case report and literature review. Int J Clin Exp Pathol. 2014;7:8223–6.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Schoolmeester JK, Carlson J, Keeney GL, et al. Alveolar soft part sarcoma of the female genital tract. Am J Surg Pathol. 2017;41:622–32.CrossRefGoogle Scholar
  49. 49.
    Roma AA, Yang B, Senior MR, et al. TFE3 immunoreactivity in alveolar soft part sarcoma of the uterine cervix: a case report. Int J Gynecol Pathol. 2005;24:131–5.CrossRefGoogle Scholar
  50. 50.
    Jabbour MN, Seoud M, Al-Ahamadie H, et al. ASPL-TFE3 translocation in vulvovaginal alveolar soft part sarcoma. Int J Gynecol Pathol. 2014;33:263–7.CrossRefPubMedGoogle Scholar
  51. 51.
    Colombat M, Sevestre H, Gontier MF. Epithelioid leiomyosarcoma of the uterine cervix. Report of a case. Ann Pathol. 2001;21:48–50.PubMedGoogle Scholar
  52. 52.
    Gotoh T, Kikuchi Y, Takano M, et al. Epithelioid leiomyosarcoma of the uterine cervix. Gynecol Oncol. 2001;82:400–5.CrossRefPubMedGoogle Scholar
  53. 53.
    Fujiwaki R, Yoshida M, Iida K, et al. Epithelioid leiomyosarcoma of the uterine cervix. Acta Obstet Gynecol Scand. 1998;77:246–8.PubMedGoogle Scholar
  54. 54.
    Fraga M, Prieto O, Garcia-Caballero T, et al. Myxoid leiomyosarcoma of the uterine cervix. Histopathology. 1994;25:381–4.CrossRefPubMedGoogle Scholar
  55. 55.
    Abdul-Karim FW, Bazi TM, Sorensen K. Sarcoma of the uterine cervix: clinicopathologic findings in three cases. Gynecol Oncol. 1987;26:103–11.CrossRefPubMedGoogle Scholar
  56. 56.
    Zhiqiang L, Bin S, Min F, et al. Leiomyosarcoma of cervical stump following subtotal hysterectomy: a case report and review of literature. Eur J Gynecol Oncol. 2016;37:148–51.Google Scholar
  57. 57.
    Bell SW, Kempson RL, Hendrickson MR. Problematic uterine smooth muscle neoplasms. A clinicopathological study of 213 cases. Am J Surg Pathol. 1994;18:535–58.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Bernstein HB, Broman JH, Apicelli A, et al. Primary malignant schwannoma of the uterine cervix: a case report and literature review. Gynecol Oncol. 1999;74:288–92.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Keel SB, Clement PB, Prat J, et al. Malignant schwannoma of the uterine cervix: A study of three cases. Int J Gynecol Pathol. 1998;17:223–30.CrossRefGoogle Scholar
  60. 60.
    Mills AM, Karamchandani JR, Vogel H, et al. Endocervical fibroblastic malignant peripheral nerve sheath tumour (neurofibrosarcoma): report of a novel entity possibly related to endocervical CD34 fibrocytes. Am J Surg Pathol. 2011;35:404–12.CrossRefPubMedGoogle Scholar
  61. 61.
    Horn LC, Fischer U, Bilek K. Primitive neuroectodermal tumor of the cervix uteri. A case report. Gen Diagn Pathol. 1997;142:227–30.PubMedGoogle Scholar
  62. 62.
    Pauwels P, Ambros P, Hattinger C, et al. Peripheral primitive neuroectodermal tumour of the cervix. Virchows Arch. 2000;436:68–73.CrossRefPubMedGoogle Scholar
  63. 63.
    Malpica A, Moran CA. Primitive neuroectodermal tumor of the cervix: A clinicopathologic and immunohistochemical study of two cases. Ann Diagn Pathol. 2002;6:281–7.CrossRefPubMedGoogle Scholar
  64. 64.
    Snijders-Keilholz A, Ewing P, Seynaeve C, Burger CW. Primitive neuroectodermal tumor of the cervix uteri: a case report-changing concepts in therapy. Gynecol Oncol. 2005;98:516–9.CrossRefPubMedGoogle Scholar
  65. 65.
    Chiang S, Snuderi M, Kojiro-Sanada S, et al. Primitive neuroectodermal tumours of the female genital tract. Am J Surg Pathol. 2017;41(6):761–72.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Kudela E, Biringer K, Kasajova P, et al. Perivascular epithelioid tumours of the uterine cervix. Pathol Res Pract. 2016;212:667–71.CrossRefPubMedGoogle Scholar
  67. 67.
    Liu F, Zhang R, Wang Z-Y, et al. Malignant perivascular epithelioid cell tumor (PEComa) of cervix with TFE3 gene rearrangement: a case report. Int J Clin Exp Pathol. 2014;7:6409–14.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Tajima S, Koda K. Perivascular epithelioid cell tumour of the uterine cervix identified on a conventional cervical smear. Diagn Cytopathol. 2015;43:1011–6.CrossRefPubMedGoogle Scholar
  69. 69.
    Thway K, Fisher C. PEComa: morphology and genetics of a complex tumour family. Ann Diagn Pathol. 2015;19:359–68.CrossRefPubMedGoogle Scholar
  70. 70.
    Ohayi SA, Ezugwu EC, Aderibigbe AS, et al. Angiosarcoma of the cervix: a case and literature review. Niger J Med. 2013;22:362–4.Google Scholar
  71. 71.
    Doldan A, Otis CN, Pantanowitz L. Adipose tissue: a normal constituent of the uterine cervical stroma. Int J Gynecol Pathol. 2009;28:396–400.CrossRefGoogle Scholar
  72. 72.
    Tandon B, Hagemann IS, Maluf HM, et al. Association of Li Fraumeni syndrome with small cell carcinoma of the ovary, hypercalcemic type and concurrent pleomorphic liposarcoma of the cervix. Int J Gynecol Pathol. 2017;36:593–9.CrossRefGoogle Scholar
  73. 73.
    Suarez-Zamora A, Barrera-Herrera LE, Rodriguez-Urrego PA. Proximal-type epithelioid sarcoma: report of an unusual case in the uterine cervix. Int J Surg Path. 2017;25:468–7471.CrossRefGoogle Scholar
  74. 74.
    Jeney H, Heller DS, Hameed M, et al. Epithelioid sarcoma of the uterine cervix. Gynecol Oncol. 2003;89:536–9.CrossRefGoogle Scholar

Copyright information

© Science Press & Springer Nature Singapore Pte Ltd.  2019

Authors and Affiliations

  1. 1.Birmingham Women’s HospitalBirminghamUK

Personalised recommendations