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.

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 diff. (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[10]

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.

AIS

  • Diagnosis of AIS dependent primarily on nuclear changes:[11]
    • Nuclear crowding.
    • Nuclear hyperchromasia.
    • Cigar-shaped nuclei.
    • +/-Mitoses.
  • Cytoplasm.
    • Hyperchromasia.

Invasive

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.

IHC

Uterus vs. cervix:[12]

  • 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.[13]

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. Jan 2009.
  7. ↑ STC. Jan 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. ↑ NEED REF.
  11. ↑ need ref
  12. ↑ LAE 15 Jan 2009.
  13. ↑ 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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