Uterine cervix

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The cervix, or uterine cervix to be more precise, 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 cervix is dealt with in the gynecologic cytopathology article.

Introduction

  • Consists of non-keratinized squamous epithelium and simple columnar epithelium.
  • The area of overlap (between squamous & columnar) is known as the "transformation zone".[1]
    • Also known as "transition zone".
  • Most cervix cancer is squamous cell carcinoma.

Common benign

Nabothian cyst

  • Simple endocervical cyst.
    • Lined by endocervical epithelial cells.
      • Columnar morphology with large clear, apical vacuoles.

Image:

Tunnel cluster

  • Benign proliferation of endocervical glands[2]
  • Important only as one could mistake minimal deviation adenocarcinoma for it. (???)

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.

Endocervical glands

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

  • If the nuclei are columnar think cancer! This is like in the colon-- columnar nuclei = badness.

Mnemonic: The Cs (Cervix & Colon) are similar.

Cervical intraepithelial neoplasia (CIN)

Refers to changes in squamous epithelium.

Grades (squamous intraepithelial neoplasia):

  • CIN I = mild dysplasia.
  • CIN II = moderate dysplasia.
  • CIN III = severe dysplasia.

Bethesda system:

  • LSIL (low-grade squamous intraepithelial lesion) = CIN I.
  • HSIL (high-grade squamous intraepithelial lesion) = CIN II, CIN III.

Treatment

  • LSIL: nothing, as usually regress.
  • HSIL: excision (e.g. cone, LEEP, laser) + followup.

LEEP = Loop Electrosurgical Excision Procedure (LEEP) Procedure.

  • Used for squamous lesions -- pathologist typically gets several pieces.

Cone

  • Used for endocervical lesions, i.e. adenocarcinoma in situ (AIS).
  • Pathologist gets a ring or donut-shaped piece of tissue.

Histologic changes in CIN I, CIN II and CIN III

  • CIN I = cytoplasmic halos (koilocytic atypia), atypical cells close to basement membrane only.
    • 3:1 enlargement of nucleus vs. normal.[3]
    • Binucleation may be seen (cytopathic effect of HPV).[4]
  • CIN II = increased nuclear-cytoplasmic ratio, loss of polarity, incr. mitoses, hyperchromasia.
    • If there are large nuclei... you should seen 'em on low power, i.e. 25x.
  • CIN III = same changes as in CIN II + outer third (or full thickness).

Ref.:[5]

Notes:

  • Hyperchromasia is a very useful feature for identifying CIN (particularly at low power, i.e. 25x).
  • Kiolocytes are the key feature of CIN I.
  • Kiolocytes are not considered to be part of a CIN II lesion or CIN III lesion.
  • Large irregular nuclei are not required for CIN II... but you should think about it.
  • Some mild changes at the squamo-columnar junction are expected.
  • Look for the location of mitoses...
    • If there is a mitosis in the inner third (of the epithelial layer) = at least CIN I.
    • If there is a mitosis in the middle third (of the epithelial layer) = at least CIN II.
    • If there is a mitosis in the outer third = CIN III.
  • Nucleoli are usually NOT present in CIN.[6]
    • Nucleoli are common in reactive changes.[7]

Kiolocytes versus benign squamous

Kiolocytes:

  • Perinuclear clearing.
  • Nuclear changes.
    • Size similar (or larger) to those in the basal layer of the epithelium.
    • Nuclear enlargement should be evident on low power, i.e. 25x. [8]
    • Central location - nucleus should be smack in the middle of the cell.

Notes:

  1. Both perinuclear clearing and nuclear changes are essential.
  2. Benign cells have a small nucleus that is peripheral.

Cervix cancer grading

  1. Well-differentiated (keratinizing).
  2. Moderately differentiated (nonkeratinizing).
  3. Poorly differentiated.

Ref.:[9]

SCC of the cervix versus CIN III

Invasive cancer look for:

  • Eosinophilia.
  • Extra large nuclei, i.e. nuclei 5x normal size.
  • Stromal inflammation (lymphocytes, plasma cells).
  • Long rete ridges.
  • Numerous beeds/blobs of epithelial cells that seem unlikely to be rete ridges.
  • Desmoplastic stroma - increased cellularity, spindle cell morphology.

Pitfalls:

  • Squamous metaplasia.
    • If you can trace the squamous cells from a gland to the surface it is less likely to be invasive cancer.

See: http://www.nature.com/modpathol/journal/v15/n3/pdf/3880520a.pdf

Squamous metaplasia

Squamous metaplasia is a response to inflammation...

  • Nuclei are uniform size and round.
  • Intercellular bridges are often seen/edema is often seen.
  • Uniform cell spacing, i.e. NO crowding.
  • NEGATIVES:
    • No mitoses (think cancer/CIN if you see 'em).
    • Usually no hyperchromatism (think cancer/CIN if you see it).

Notes:

  • It is possible to confuse CIN III with squamous metaplasia.

IHC:

  • p16 (poor man's test for HPV).
  • Ki-67 (proliferation marker).

Adenocarcinoma

  • Adenocarcinoma of the cervix/adenocarcinoma in situ (AIS) of the cervis is much less common than squamous dysplasia of the cervix/SCC of the cervix.
  • AIS/adenocarcinoma arises can arise from the endocervical glands.

Adenocarcinoma in situ (AIS)

  • Diagnosis of AIS dependent primarily on nuclear changes:
    • Nuclear crowding.
    • Nuclear hyperchromasia.
    • Cigar-shaped nuclei.
    • +/-Mitoses.
  • Cytoplasm.
    • Hyperchromasia.

Invasive adenocarcinoma

Features:

Notes:

  • AIS changes - similar to colonic dysplasia.
  • AIS may occur together with CIN.
    • not infrequently they (AIS, CIN) occur together - both are due, indirectly, to HPV infection.
  • May be difficult to be certain of invasion.

IHC

Uterus vs. cervix:[10]

  • Cervix (typically): CEA+, p16+.
    • ... and ER-, PR-, vimentin-.
  • Uterus (typically): vimentin+, ER+, PR+.
    • ... and CEA-, p16-.

Uncommon types of cervical cancer

There are a number of uncommon type of cervical cancer.

Adenosquamous carcinoma

A mixed of morphologic features seen in squamous carcinoma and adenocarcinoma.

Image: Adenosquamous carcinoma (WC).

Clear cell carcinoma

Associated with diethylstilbestrol exposure in utero.[11]

See also

References

  1. ↑ URL: http://www.med-ed.virginia.edu/Courses/path/gyn/cervix1.cfm. Accessed on: 12 May 2010.
  2. ↑ http://pathologyoutlines.com/cervix.html#tunnelclusters
  3. ↑ [need ref]
  4. ↑ [need ref]
  5. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1075-6. ISBN 0-7216-0187-1.
  6. ↑ STC. January 2009.
  7. ↑ STC. January 2009.
  8. ↑ V. Dube 2008.
  9. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1077. ISBN 0-7216-0187-1.
  10. ↑ LAE. 15 January 2009.
  11. ↑ van Dijck, JA.; Doorduijn, Y.; Bulten, JH.; Verloop, J.; Massuger, LF.; Kiemeney, BA. (2009). "[Vaginal and cervical cancer due to diethylstilbestrol (DES); end epidemic]". Ned Tijdschr Geneeskd 153: A366. PMID 19857300.
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