Cervix

Contributed by Yevgen Chornenkyy, M.D., M.Sc. and Bonnie Choy, M.D.


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• Squamous metaplasia:
  • Less nuclear enlargement and lower N/C ratio
  • Minimal to mild nuclear membrane abnormalities
  • If reactive, may have nucleoli
• Transitional cell metaplasia:
  • Characteristic nuclear morphology showing longitudinal grooves (frequent coffee bean shaped nuclei suggest metaplastic changes)
  • Minimal hyperchromasia
• Tubal metaplasia:
  • Apical terminal bar and cilia
  • Same sized nuclei as squamous metaplastic nuclei
  • Basally placed nucleus with smooth nuclear contours
  • May have higher N/C ratio than normal endocervical cells
• Endometrial cells:
  • Exfoliated:
    • Degenerated, small nuclei with high N/C ratio
    • Small nucleoli may been seen
    • Apoptotic bodies may been present within shedding endometrial groups
  • Directly sampled:
    • Nuclei slightly larger than those of intermediate cells
    • Lower N/C ratio
    • Smooth nuclear membranes
    • Maintain nuclear polarity when seen in clusters with associated endometrial stromal cells
• Endocervical cells:
  • Presence of small nucleoli
  • Finely granular and evenly distributed chromatin
  • Smooth nuclear contours
  • Granular or finely vacuolated cytoplasm, occasionally with some elongation
  • Exfoliated cells may have rounded up appearance and high N/C ratio
  • Retain columnar cytoplasmic configuration with eccentrically placed nuclei
• Endocervical polyp atypia:
  • Single cells with highly atypical and hyperchromatic nuclei
  • Correlation with clinical history and histology is important
• IUD effect:
  • Variable amount of cytoplasm and N/C ratio
  • Degenerative nuclei with wrinkled or smudgy dark chromatin
  • Vacuolated cytoplasm, may have signet ring appearance
• Atrophy:
  • Variable N/C ratio
  • Chromatin is uniformly distributed and finely textured
  • Nuclear contour / membrane is smooth
  • Smudgy or degenerated nuclear chromatin
  • No mitoses
• Decidualized stromal cells:
  • More granular, less dense cytoplasm
  • Prominent basophilic nucleolus
  • Lack of any evidence of HPV cytopathic effect
  • Larger nucleus and higher N/C ratio can mimic HSIL
  • Clinical history of pregnancy
• Atypical squamous cells, cannot exclude HSIL (ASC-H):
  • Recommended in cases with cells showing features of squamous metaplasia and nuclear atypia for which it is difficult / impossible to exclude HSIL
• Atypical squamous cells of undetermined significance (ASC-US) associated with atrophy:
  • Recommended in cases with marked squamous atypia associated with atrophy that is difficult / impossible to distinguish from HSIL
• Adenocarcinoma in situ (AIS):
  • Hyperchromatic nuclei with fine to coarse chromatin
  • Nuclear membrane irregularities and notching
  • High N/C ratio
  • Feathering or rosette formation
• Squamous cell carcinoma:
  • Prominent nucleoli
  • Irregular chromatin distribution
  • Necrotic debris
• Inflammatory cells:
  • Histiocytes:
    • Small to medium sized, oval kidney bean nuclei
    • Sometimes prominent longitudinal groove
    • Finely textured, normochromatic
    • Abundant foamy vacuolated cytoplasm
  • Lymphocytes:
    • Small round nuclei with coarse chromatin to larger nuclei with open chromatin
    • Minimal cytoplasm
    • May be seen with tingible body macrophages, plasma cells and dendritic cells

A 37 year old woman with a previous history of recent pregnancy, recurrent sexually transmitted infections, intrauterine device use, persistent high risk HPV and LSIL, undergoes cervical cytology testing as part of her routine preventative health care visit. Cytomorphology is shown in the image above. Taking into account the clinical and cytomorphological findings, what is the most correct diagnosis?

1. Atrophic changes
2. High grade squamous intraepithelial lesion (HSIL)
3. Intrauterine device related changes
4. Tubal metaplasia

B. High grade squamous intraepithelial lesion (HSIL). High grade squamous intraepithelial lesion (HSIL) changes consist of immature, delicate or metaplastic cytoplasm. The nuclear features generally contain high N/C ratios, nuclear envelope irregularities and generally hyperchromatic nuclei, although hypochromatic forms can be present. The chromatin is usually evenly dispersed. Nucleoli are generally absent but can be seen when HSIL extends into endocervical gland spaces or in the background of reactive or reparative change. Atrophic changes (A) generally have a clinical history of advanced age or menopause. The morphologic features include variable N/C ratio, degenerated nuclear chromatin, smooth nuclear membranes and no mitotic activity. Intrauterine device related changes (C): while this patient has history of IUD use, she also has history significant for LSIL and positive hrHPV increasing pretest probability for HSIL. Generally IUD changes consist of degenerative nuclei, smudgy dark chromatin and vacuolated cytoplasm. Tubal metaplasia (D) is an HSIL mimic and generally contains apical terminal bar and cilia, nuclear size roughly similar to squamous metaplastic cells, basally located nucleus, smooth nuclear contours and can have higher N/C ratios than normal endocervical cells.

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Reference: HSIL cytology

A 47 year old woman taking medication for HIV / AIDS undergoes cervical cytology testing. The image is shown above. What is the most likely diagnosis?

1. Atrophy
2. High grade squamous intraepithelial lesion (HSIL)
3. Low grade squamous intraepithelial lesion (LSIL)
4. Tubal metaplasia

B. High grade squamous intraepithelial lesion (HSIL). An immunocompromised state increases a patient's risk of persistent infection and development of a squamous intraepithelial lesion (SIL). Specifically, smoking, immunosuppression (e.g. transplant or human immunodeficiency virus [HIV / AIDS]) or radiation therapy are risk factors for low grade squamous intraepithelial lesions (LSIL) progression to HSIL. In this example, HSIL cells demonstrate delicate cytoplasm, variation of nuclear size and shape, nuclear grooves, nuclear envelope irregularities and abnormal chromatin. Low grade squamous intraepithelial lesion (LSIL) (C) would be expected to have lower nuclear to chromatin ratio (for nuclear enlargement more than ≥ 3, the area of normal intermediate nuclei results in a slightly increase nuclear to cytoplasmic ratio), mature cytoplasm, koilocytic change (perinuclear cavitation consisting of a broad, sharply delineated clear perinuclear zone and a peripheral rim of densely stained cytoplasm). Atrophy (A) distinguishing features are absent. These include clinical history of menopause or advanced age, uniformly distributed chromatin, smooth nuclear contours, nuclear to chromatin ratio can be increased, degenerated nuclear chromatin, no mitoses. Tubal metaplasia (D) is an HSIL mimic and generally contains apical terminal bar and cilia, nuclear size roughly similar to squamous metaplastic cells, basally located nucleus, smooth nuclear contours and can have higher N/C ratios than normal endocervical cells.

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Reference: HSIL cytology