Uterine cervix

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The uterine cervix, also simply cervix, is the gateway to the uterine corpus. It is not infrequently afflicted by cancer -- squamous cell carcinoma. Prior to routine Pap tests it was a leading cause of cancer death in women in the Western world.

Polyps associated with the cervix are discussed the cervical polyp article.

Cytopathology of the uterine cervix is dealt with in the gynecologic cytopathology article.

Contents

Introduction

Overview

  • Most cervix cancer is squamous cell carcinoma.
  • The work-up of a suspicious Pap test is a colposcopic examination and biopsies, which are the topic of this article.

Indications for coloposcopic exam (based on the ASCCP Consensus Guidelines of 2001):[1]

Colposcopic examination

  • Performed by gynecologists.
  • Exam usually includes a search for acetowhite epithelium (AWE); this is accomplished by the application of acetic acid (to help identify lesions for biopsy).
  • Cervical ectropian (AKA cervical eversion, AKA ectropian) = endocervical epithelium at external os, considered benign, grossly has a granulation tissue-like appearance.[4]

Cervical specimens

Cytology

Biopsies

The types of biopsies that are done are:

  1. Cervical biopsies - prompted by abnormal Pap test, e.g. HSIL, to look for squamous cell carcinoma of the uterine cervix.
  2. Endocervical curettage (ECC) - to work-up columnar dysplasia, e.g. endocervical adenocarcinoma/endometrial adenocarcinoma.

Surgical specimens

  1. Loop electrosurgical excision procedure (LEEP).
    • AKA large loop excision of the transformation zone (LLETZ).[5][6]
  2. Radical trachelectomy - removal of the uterine cervix and parametria, preserves fertility.
  3. Radical hysterectomy - advanced cervical carcinoma (Stage IA2 and Stage IB1), recurrent carcinoma.[7]

Other

Normal histology

Features:

  • The uterine cervix consists of non-keratinized squamous epithelium and simple columnar epithelium.
  • The area of overlap (between squamous & columnar) is known as the "transformation zone".[8]
    • Also known as "transition zone".

Notes:

  • Considered from the perspective of histology:
    • The squamous component is referred to as the exocervix (or ectocervix[9]).
    • The simple columnar (or glandular) component is referred to as the endocervix.

Images:

Negative LEEP

Transformation zone - biopsy

Microscopic

Features:

  • Small round cells.
  • Usually no halos.
    • May be seen in pseudokoilocytes.
  • No nuclear membrane irregularities.
  • No nuclear hyperchromasia.

Images

www:

Sign out

UTERINE CERVIX, BIOPSY: 
- TRANSFORMATION ZONE WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR DYSPLASIA.
UTERINE CERVIX, BIOPSY:
- SQUAMOUS MUCOSA WITHOUT APPARENT PATHOLOGY.
- STRIPPED ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY.
- NEGATIVE FOR DYSPLASIA.

Endocervical glands

Microscopic

Features: Cervical glands normally have round nuclei and vaguely resemble the colonic mucosa.

Notes:

  • If the nuclei are columnar think cancer! This is like in the colon-- columnar nuclei = badness.
    • Memory device: The Cs (Cervix & Colon) are similar.
  • Endocervical epithelium (ECE) has a morphology similar to the epithelium of secretory phase endometrium (SPE):
    • ECE - grey foamy appearing cytoplasm.
    • SPE - eosinophilic cytoplasm.
      • Most useful feature to differentiate ECE and SPE is the accompanying stroma.

Sign out

UTERINE ENDOCERVIX, CURETTAGE: 
- ENDOCERVICAL MUCOSA AND STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS. 

Inflamed with squamous epithelium

UTERINE ENDOCERVIX, CURETTAGE:
- BENIGN STRIPPED ENDOCERVICAL EPITHELIUM AND SCANT INFLAMED ENDOCERVICAL MUCOSA.
- VERY SCANT SUPERFICIAL SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.

Squamous epithelium present

UTERINE ENDOCERVIX, CURETTAGE: 
- ENDOCERVICAL MUCOSA WITHIN NORMAL LIMITS. 
- SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.

Endometrium present

UTERINE ENDOCERVIX, CURETTAGE: 
- ENDOCERVICAL MUCOSA WITHIN NORMAL LIMITS. 
- SCANT NON-PROLIFERATIVE ENDOMETRIUM.

Inflamed

UTERINE ENDOCERVIX, CURETTAGE: 
- INFLAMED ENDOCERVICAL MUCOSA. 
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR MALIGNANCY.
UTERINE ENDOCERVIX, CURETTAGE:
- BENIGN INFLAMED ENDOCERVICAL MUCOSA.
- STRIPPED ENDOCERVICAL EPITHELIUM WITHIN NORMAL LIMITS.

No stroma present

UTERINE ENDOCERVIX, CURETTAGE: 
- STRIPPED ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY. 

Limited tissue

UTERINE ENDOCERVIX, CURETTAGE:
- ONE MINUTE FRAGMENT OF ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY,
SEE COMMENT.
- VERY SCANT SUPERFICIAL SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.

COMMENT:
The assessment is severely limited by the small amount of tissue. A re-biopsy
should be considered within the clinical context.
UTERINE ENDOCERVIX, CURETTAGE:
- ONE MINUTE FRAGMENT OF ENDOCERVICAL EPITHELIUM WITHOUT APPARENT PATHOLOGY,
SEE COMMENT.
- VERY SCANT SUPERFICIAL SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.

COMMENT:
The assessment is severely limited by the small amount of tissue. Clinical correlation is
suggested.
UTERINE ENDOCERVIX, CURETTAGE:
- BENIGN SQUAMOUS EPITHELIUM WITH METAPLASTIC CHANGE.
- VERY SCANT BENIGN ENDOCERVICAL EPITHELIUM, SUBOPTIMAL SAMPLING.
UTERINE CERVIX, BIOPSY:
- MINUTE FRAGMENTS OF SUPERFICIAL SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.
- SCANT MUCOUS AND INFLAMMATORY CELLS.
- SEE COMMENT.

COMMENT:
The assessment is severely limited by the small amount of tissue. A re-biopsy should be
considered within the clinical context.

Inadequate biopsy

  • Unfortunately, inadequate biopsies are common.

Endocervix

Sign out

No endocervical epithelium

UTERINE ENDOCERVIX, CURETTAGE: 
- SQUAMOUS EPITHELIUM WITHOUT APPARENT PATHOLOGY.
- NO ENDOCERVICAL EPITHELIUM IDENTIFIED.
- MUCOUS AND INFLAMMATORY CELLS.

No epithelium

UTERINE ENDOCERVIX, CURETTAGE: 
- MUCOUS AND INFLAMMATORY CELLS.
- NO EPITHELIUM IDENTIFIED.

No tissue

UTERINE ENDOCERVIX, CURETTAGE: 
- NO TISSUE PRESENT, SEE COMMENT. 

COMMENT: 
No tissue identified on gross or microscopy.
UTERINE ENDOCERVIX, CURETTAGE:
- NO TISSUE PRESENT, SEE COMMENT.

COMMENT:
No tissue identified on microscopy. No tissue is seen on inspection of the paraffin block.

Where to start

  1. Identify epithelium - exocervical (stratified squamous), endocervical (simple columnar), both.
    • If there is both exocervix and endocervix --> transition zone.
  2. Identify possible squamous lesions.
  3. Identify possible endocervical lesions.

Benign entities of the cervix

The cervix is MANTLED:

Benign

Nabothian cyst

General

  • Benign.
  • Common.

Gross

  • Bump.
  • Pale colour.

DDx - clinical:

Image

Microscopic

Features:

  • Simple endocervical cyst.
    • Usually lined by endocervical epithelial cells - may be flattened.
      • Columnar morphology with large clear, apical vacuoles.
    • +/-Macrophages.
    • +/-Mucus.

Note:

Image:

Sign out

CERVICAL POLYP, REMOVAL:
- BENIGN POLYPOID FRAGMENT OF EXOCERVICAL MUCOSA WITH NABOTHIAN CYSTS AND 
BENIGN ENDOCERVICAL EPITHELIUM.
POLYPOID LESION ("CERVICAL POLYP"), EXCISION:
- POLYPOID NABOTHIAN CYST.

Tunnel cluster

General

Microscopic

Features:[13][14]

  • Well-circumscribed lesion consisting of:
  • Benign endocervical glands.
    • Dilated & filled with mucin or (less commonly) eosinophilic secretions.
    • Lining epithelium compressed/flattened (attenuated).
    • Gland architecture: branching, tortuous.
    • Scant intervening stroma.

Notes:

  1. Usually no nuclear atypia and no mitotic activity.
  2. Important only as one could possibly mistake it as minimal deviation adenocarcinoma, AKA adenoma malignum.[15]

Images

www:

Microglandular hyperplasia

Not to be confused with microglandular adenosis.
  • Abbreviated MGH.
  • AKA microglandular change.

Wolffian duct hyperplasia

General

  • Benign.

Microscopic

Features:

  • Abundant small tubules with a simple cuboidal epithelium.
  • Round small bland nucleus.

DDx:

Stains

Squamous metaplasia of the uterine cervix

  • Abbreviated SMC.

Reactive squamous epithelium of the uterine cervix

  • AKA reactive squamous epithelium.
  • AKA reactive changes.

General

  • Common.
  • Individuals with persistent inflammation on Pap test may have occult SIL.[16]

Microscopic

Features:

  1. Inflammation - key feature.
    • Lymphocytes.
    • Plasma cells.
  2. Mild nuclear enlargement. †
  3. Nucleoli - important.

Note:

  • † Normal squamous cell nuclei are approximately 8 μm.[17]
    • Mild enlargement ~ 2-3x normal.
    • CIN I nuclei are ~ 3x normal (24 μm).

DDx:

IHC

  • p16 -ve.

Sign out

UTERINE CERVIX, BIOPSY:
- REACTIVE SQUAMOUS EPITHELIUM.
- BENIGN ENDOCERVICAL GLANDS.
- NEGATIVE FOR MALIGNANCY.
COMMENT:
The squamous epithelium is negative for p16 staining. Ki-67 staining is predominantly in
the lower third of the epithelium.

Tubal metaplasia of the uterine cervix

  • AKA tubal metaplasia, abbreviated TM.

General

  • Benign.
  • Mimics the appearance of AIS - especially at low power.

Microscopic

Features - like the fallopian tube:

  • Nuclear crowding vis-à-vis benign endocervical epithelium (low power).
  • Mixed cell population (high power):
    • Peg cells - "tall" and "skinny".
      • Columnar/golf tee-like appearance.
    • Ciliated cells - cilia, pale cytoplasm, round central nucleus.
    • Secretory cells - non-ciliated, basophilic cytoplasm, round small basal nuclei.

DDx:

Image:

IHC

Features:[18]

Atrophy of the uterine cervix

  • AKA cervical atrophy.
  • AKA atrophy of the cervix.
  • AKA cervix with atrophic changes.

Radiation changes of the endocervical epithelium

General

  • Uncommon.
  • Clinical history: radiation treatment for cervical carcinoma.[19]

Microscopic

Features:[19]

  • Nuclear enlargement with a normal NC ratio.
  • +/-Coarse chromatin.
  • +/-Nucleoli.
  • +/-Multinucleation - very common.
  • Histiocytes - common.

Reactive endocervical cells

General

  • Benign.

Microscopic

Features:

  • Mild nuclear enlargement.
  • +/-Multinucleation.[20]

Notes: DDx of multinucleated endocervical cells:

  • HSV.[21]
  • Benign endocervical cells.

Images

www:

Non-invasive

Cervical intraepithelial neoplasia

  • Previously known as cervical intraepithelial neoplasia and cervical dysplasia.

Endocervical adenocarcinoma in situ

For the cytology see Gynecologic cytopathology#Endocervical adenocarcinoma in situ
  • AKA adenocarcinoma in situ, abbreviated AIS.

Cancer

Squamous cell carcinoma of the uterine cervix

  • AKA cervical squamous cell carcinoma.

Adenocarcinoma of the uterine cervix

  • AKA endocervical adenocarcinoma.
  • AKA cervical adenocarcinoma.

Uncommon non-invasive

Stratified mucin-producing intraepithelial lesions of the cervix

  • Abbreviated SMILE (Stratified Mucin-producing Intraepithelial LEsion).

Uncommon types of cervical cancer

There are a number of uncommon type of cervical cancer.

Serous carcinoma of the uterine cervix

General

  • Poor prognosis.[22]
  • Extremely rare.

Microscopic

Features:

Adenosquamous carcinoma of the uterine cervix

Clear cell carcinoma of the uterine cervix

Small cell carcinoma of the cervix

  • Like small cell carcinoma elsewhere.

DDx:

IHC

  • HPV +ve.

Adenoid basal carcinoma

See also: Basal cell carcinoma.

General

Microscopic

Features:[23]

  • Nests of cells with basaloid rim and squamoid center.
    • Basaloid cells look benign.

DDx:

Image:

Glassy cell carcinoma

Villoglandular adenocarcinoma of the cervix

  • AKA well-differentiated papillary villoglandular adenocarcinoma,[24] AKA villoglandular papillary adenocarcinoma, AKA well-differentiated villoglandular adenocarcinoma.

General

  • Rare.
  • Younger patients and relatively good prognosis.[25]
  • Associated with HPV.
  • May also arise from the endometrium.[26]

Microscopic

Features:[27]

  • Papillary structures (nipple-like shapes with a fibrovascular core) that are long.
    • Nobody defines "long".
      • Perhaps - long >3:1 length:width.
  • Covered by columnar (or cuboidal) epithelium.
  • Intracellular mucin (focal).

DDx:

  • Serous carcinoma of the cervix.

Images

www:

Mucoepidermoid carcinoma of the uterine cervix

General

  • Controversial - not in the WHO.[28]

Microscopic

Features:[29]

  • Squamous cell carcinoma-like with:
    1. No glands formation.
    2. Intracellular mucin.
      • Classically have mucous cells - cells with abundant fluffy cytoplasm and large mucin vacuoles - key feature.

Notes:

DDx:

Stains

Mucin stains:[29]

IHC

Molecular

Like the salivary gland tumour:

  • t(11;19) CRTC1/MAML2.[28]

Mesonephric adenocarcinoma

General

Microscopic

Features:[30]

  • Nuclear atypia - key feature.
    • Nuclear crowding.
  • Variable architecture:
    • Tubular, papillary, solid, retiform (net-like[31]).

DDx:

IHC

Features:[30]

  • CK7 +ve.
  • CD10 +ve.

Others:[30]

  • CK20 -ve.
  • ER -ve.
  • PR -ve.
  • CEA -ve.

Minimal deviation adenocarcinoma of the uterine cervix

  • AKA adenoma malignum.
  • AKA minimal deviation adenocarcinoma, abbreviated MDA.

See also

References

  1. Dresang, LT.. "Colposcopy: an evidence-based update.". J Am Board Fam Pract 18 (5): 383-92. PMID 16148248.
  2. Zonios, G. (Aug 2012). "Reflectance model for acetowhite epithelium.". J Biomed Opt 17 (8): 87003-1. doi:10.1117/1.JBO.17.8.087003. PMID 23224202.
  3. Li, W.; Venkataraman, S.; Gustafsson, U.; Oyama, JC.; Ferris, DG.; Lieberman, RW.. "Using acetowhite opacity index for detecting cervical intraepithelial neoplasia.". J Biomed Opt 14 (1): 014020. doi:10.1117/1.3079810. PMID 19256708.
  4. Casey, PM.; Long, ME.; Marnach, ML. (Feb 2011). "Abnormal cervical appearance: what to do, when to worry?". Mayo Clin Proc 86 (2): 147-50; quiz 151. doi:10.4065/mcp.2010.0512. PMC 3031439. PMID 21270291. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3031439/.
  5. Kenwright, D.; Braam, G.; Maharaj, D.; Langdana, F. (Jan 2012). "Multiple levels on LLETZ biopsies do not contribute to patient management.". Pathology 44 (1): 7-10. doi:10.1097/PAT.0b013e32834d7b5d. PMID 22173237.
  6. URL: http://www.webmd.com/cancer/cervical-cancer/loop-electrosurgical-excision-procedure-leep-for-abnormal-cervical-cell-changes. Accessed on: 20 March 2014.
  7. Ware, RA.; van Nagell, JR. (2010). "Radical hysterectomy with pelvic lymphadenectomy: indications, technique, and complications.". Obstet Gynecol Int 2010. doi:10.1155/2010/587610. PMID 20871657.
  8. URL: http://www.med-ed.virginia.edu/Courses/path/gyn/cervix1.cfm. Accessed on: 12 May 2010.
  9. URL: http://www.cancer.org/cancer/cervicalcancer/detailedguide/cervical-cancer-what-is-cervical-cancer. Accessed on: 27 January 2014.
  10. Nucci, MR. (Oct 2002). "Symposium part III: tumor-like glandular lesions of the uterine cervix.". Int J Gynecol Pathol 21 (4): 347-59. PMID 12352183.
  11. Zaino, RJ. (Mar 2000). "Glandular lesions of the uterine cervix.". Mod Pathol 13 (3): 261-74. doi:10.1038/modpathol.3880047. PMID 10757337.
  12. Okamoto, Y.; Tanaka, YO.; Nishida, M.; Tsunoda, H.; Yoshikawa, H.; Itai, Y.. "MR imaging of the uterine cervix: imaging-pathologic correlation.". Radiographics 23 (2): 425-45; quiz 534-5. PMID 12640157.
  13. URL: http://pathologyoutlines.com/cervix.html#tunnelclusters. Accessed on: 27 February 2011.
  14. URL: http://surgpath4u.com/caseviewer.php?case_no=477. Accessed on: 5 September 2011.
  15. Gilks CB, Young RH, Aguirre P, DeLellis RA, Scully RE (September 1989). "Adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. A clinicopathological and immunohistochemical analysis of 26 cases". Am. J. Surg. Pathol. 13 (9): 717–29. PMID 2764221.
  16. Bhutia, K.; Puri, M.; Gami, N.; Aggarwal, K.; Trivedi, SS.. "Persistent inflammation on Pap smear: does it warrant evaluation?". Indian J Cancer 48 (2): 220-2. doi:10.4103/0019-509X.82901. PMID 21768670.
  17. URL: http://www.curran.pwp.blueyonder.co.uk/cytology.htm. Accessed on: 5 November 2012.
  18. Marques, T.; Andrade, LA.; Vassallo, J. (Jun 1996). "Endocervical tubal metaplasia and adenocarcinoma in situ: role of immunohistochemistry for carcinoembryonic antigen and vimentin in differential diagnosis.". Histopathology 28 (6): 549-50. PMID 8803599.
  19. 19.0 19.1 Frierson, HF.; Covell, JL.; Andersen, WA. (1990). "Radiation changes in endocervical cells in brush specimens.". Diagn Cytopathol 6 (4): 243-7. PMID 2209348.
  20. URL: http://www.surgpath4u.com/caseviewer.php?case_no=229. Accessed on: 2 January 2014.
  21. Naib, ZM.; Nahmias, AJ.; Josey, WE.; Zaki, SA. (Jun 1973). "Relation of cytohistopathology of genital herpesvirus infection to cervical anaplasia.". Cancer Res 33 (6): 1452-63. PMID 4352382.
  22. Togami, S.; Kasamatsu, T.; Sasajima, Y.; Onda, T.; Ishikawa, M.; Ikeda, S.; Kato, T.; Tsuda, H. (2012). "Serous adenocarcinoma of the uterine cervix: a clinicopathological study of 12 cases and a review of the literature.". Gynecol Obstet Invest 73 (1): 26-31. doi:10.1159/000329319. PMID 21876330.
  23. 23.0 23.1 Senzaki H, Osaki T, Uemura Y, et al. (December 1997). "Adenoid basal carcinoma of the uterine cervix: immunohistochemical study and literature review". Jpn. J. Clin. Oncol. 27 (6): 437–41. PMID 9438010. http://jjco.oxfordjournals.org/cgi/content/full/27/6/437.
  24. Fadare, O.; Zheng, W. (Nov 2005). "Well-differentiated papillary villoglandular adenocarcinoma of the uterine cervix with a focal high-grade component: is there a need for reassessment?". Virchows Arch 447 (5): 883-7. doi:10.1007/s00428-005-0030-3. PMID 16088403.
  25. Korach, J.; Machtinger, R.; Perri, T.; Vicus, D.; Segal, J.; Fridman, E.; Ben-Baruch, G. (2009). "Villoglandular papillary adenocarcinoma of the uterine cervix: a diagnostic challenge.". Acta Obstet Gynecol Scand 88 (3): 355-8. doi:10.1080/00016340902730359. PMID 19172445.
  26. Zaino, RJ.; Kurman, RJ.; Brunetto, VL.; Morrow, CP.; Bentley, RC.; Cappellari, JO.; Bitterman, P. (Nov 1998). "Villoglandular adenocarcinoma of the endometrium: a clinicopathologic study of 61 cases: a gynecologic oncology group study.". Am J Surg Pathol 22 (11): 1379-85. PMID 9808130.
  27. Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 180-1. ISBN 978-0443069208.
  28. 28.0 28.1 28.2 Lennerz, JK.; Perry, A.; Mills, JC.; Huettner, PC.; Pfeifer, JD. (Jun 2009). "Mucoepidermoid carcinoma of the cervix: another tumor with the t(11;19)-associated CRTC1-MAML2 gene fusion.". Am J Surg Pathol 33 (6): 835-43. doi:10.1097/PAS.0b013e318190cf5b. PMID 19092631.
  29. 29.0 29.1 29.2 Thelmo, WL.; Nicastri, AD.; Fruchter, R.; Spring, H.; DiMaio, T.; Boyce, J. (1990). "Mucoepidermoid carcinoma of uterine cervix stage IB. Long-term follow-up, histochemical and immunohistochemical study.". Int J Gynecol Pathol 9 (4): 316-24. PMID 1700969.
  30. 30.0 30.1 30.2 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 442. ISBN 978-0781765275.
  31. URL: http://www.thefreedictionary.com/retiform. Accessed on: 25 August 2012.

External links