Normal cells of the Pap test notes

Normal cells of the Pap test

  • Purpose of the lecture: establish what is normal to recognize what is abnormal in Pap tests.

  • Visual reference (drawing by Suzanne Adams):

    • Intermediate cell nuclei are present; the nucleus size is roughly 35\,
      \mu m^{2}.
    • Superficial squamous cells are polygonal with very dense pycnotic nuclei.
    • Endocervical cells can be seen on end or in a honeycomb form (groups mimicking a honeycomb).
    • Transformation zone illustrated; contains cells undergoing squamous metaplasia.
    • Some cells are more mature than others within the transformation zone.
    • Menstrual endometrial cells appear in Pap tests; these are often present around days 4\text{-}8 of the cycle and represent exodus where endometrial glands are surrounded by stromal tissue.

  • Historical context: Papnikolaou’s work reduced cervical cancer incidence over time.

    • The incidence of cervical cancer has declined with Pap testing; mortality rates have also declined.
    • Global trends: since the 1950s, cervical cancer incidence decreased by about 80\% and mortality by about 70\% in many populations due to screening.
    • Geographic disparities: WHO data published in 2015 show high rates in many third-world areas (Africa, India, parts of China, South America, Mexico) where screening is limited; global reach remains a priority.
    • Country trends: some countries show declines with screening programs (e.g., Mexico, Ecuador); in some regions (e.g., South Africa) incidence/mortality trends may still rise or require improved screening coverage.

  • Global burden and screening impact:

    • Approximately 1.3\times 10^{4} new cervical cancer cases are diagnosed each year.
    • In settings with screening, about 4.3\times 10^{3} deaths occur yearly, reflecting gaps where screening is not accessed by all women.
    • Cervical cancer tends to occur in midlife, typically around the age of 50\text{-}60 years.
    • Roughly 30% of new cervical cancer cases occur in women who have never been screened.
    • Risk factors include: family history, smoking, multiparity (multiple full-term pregnancies), HPV infection, herpes simplex virus infection, and diets low in fruits and vegetables.
    • The Pap test has reduced cervical cancer risk (incidence and mortality) since the 1950s, reinforcing the importance of screening campaigns.

  • Normal cell types observed on Pap smear:

    • Intermediate cells:
    • Nuclei are about 35\text{-}50\,\mu m^{2} in size.
    • May contain glycogen in the cytoplasm.
    • Superficial squamous cells:
    • Polygonal in shape with very dense pycnotic nuclei.
    • Endocervical cells:
    • Often found in groups alongside squamous cells; can form a honeycomb arrangement.
    • Nuclei approximately 35\text{-}50\,\mu m^{2} and cytoplasm is vacuolated with granular appearance.
    • Endocervical cells show a characteristic vacuolated cytoplasm (picket fence appearance in histology).
    • Transformation zone and squamous metaplastic cells:
    • Squamous metaplastic cells show dense, refractile cytoplasm;
      nuclei are relatively round to oval with fine, even chromatin.
    • Immature squamous metaplastic cells exhibit cytoplasmic projections; these are sometimes termed "spider cells".
    • Glycogen navicular cells:
    • Frequently seen in pregnancy and postpartum patients.
    • Parabasal cells:
    • Often observed in deep atrophy; round in shape.
    • Nuclei are regular; cytoplasm can be abundant during degenerative changes.
    • Basal, parabasal, intermediate, and superficial layers (Dame’s book depiction):
    • Basal cell layer at the base.
    • Parabasal layer just above the basal layer.
    • Intermediate cells around one-third of the way up the epithelium.
    • Superficial (top) cells occupy the uppermost layer.
    • Endocervical histology and cytology correlation:
    • Normal endocervical cells appear with a picket-fence arrangement, vacuolated cytoplasm, and nuclei in the 35\text{-}50\,\mu m^{2} range.
    • The histology shows basal cell layer with cytoplasm extending into upper layers, mirroring cytology.
    • Endometrial glands:
    • Glands are cuboidal to columnar epithelium.
    • When observed in 3D groups, they appear as roundish clusters with nuclei prominent and limited cytoplasm.

  • Background elements on the Pap test:

    • Neutrophils are commonly present in the background; presence is acceptable if not obscuring.
    • Background exudate can obscure cells and reduce sample adequacy; this is considered partially obscuring rather than satisfactory due to exudate.
    • Blood in the background is common, especially if the Pap test is collected on day 1–6 of the cycle (normal variation).
    • Doderlein's bacteria (lactic acid bacteria) can be seen in the background; they may cause cytolysis of cytoplasm, leaving cells with predominantly nuclei.

  • Atrophy and vaginitis context:

    • In atrophy (especially deep atrophy), parabasal cells predominate and background inflammatory cells may be present, a condition described as atrophic vaginitis.

  • Practical notes on interpretation:

    • Normal cells include the superficial cells with pycnotic nuclei, intermediate cells, endocervical cells, endometrial cells in appropriate contexts, and transformation zone cells.
    • Recognize background elements (neutrophils, blood, bacteria) and assess whether they obscure cellular detail enough to render the smear unsatisfactory.
    • Correlate cytology with histology: layers from basal to superficial mirror the distribution of cells seen on Pap smear (basal/parabasal, intermediate, superficial).

  • Key terms to remember:

    • Spider cells: immature squamous metaplastic cells with cytoplasmic projections.
    • Picket fence arrangement: endocervical cells arranged with vacuolated cytoplasm forming a fence-like pattern.
    • Navicular cells: glycogen-rich endocervical or cervical cells, seen in pregnancy/postpartum.
    • Atrophic vaginitis: atrophy with parabasal cells and potential background inflammation.

  • Connections to broader context:

    • The Pap test’s historical impact on public health underscores the value of screening in reducing cervical cancer incidence and mortality.
    • Understanding normal cytology aids in early detection of abnormal cells, transformation zone activity, and metaplastic changes that can mimic pathology.
    • Ethical and public health implications: equitable access to screening, addressing screening gaps in low-resource settings, and outreach to women who have never been screened.