What do wet prep clue cells represent?

Clue Cells in Wet Prep Represent Bacterial Vaginosis

Clue cells on wet prep microscopy represent a key diagnostic feature of bacterial vaginosis (BV), indicating vaginal epithelial cells covered with adherent bacteria, primarily Gardnerella vaginalis.

What Are Clue Cells?

Clue cells are vaginal epithelial cells that appear stippled or granular due to bacteria adhering to their surface. They have specific characteristics:

• Epithelial cells heavily covered with adherent bacteria, primarily Gardnerella vaginalis 1
• Cell borders appear indistinct or "fuzzy" due to bacterial coverage
• True clue cells show direct cohesive adherence of bacteria to epithelial cells, which is unique to Gardnerella species 2
• Visible on saline wet mount microscopy examination

Diagnostic Significance

Clue cells are one of the four Amsel criteria used to diagnose bacterial vaginosis:

1. Presence of clue cells on microscopic examination
2. Homogeneous, white discharge that adheres to vaginal walls
3. Vaginal pH greater than 4.5
4. Fishy odor when vaginal discharge is mixed with 10% KOH (positive whiff test) 3

The presence of at least three of these four criteria is generally considered diagnostic of bacterial vaginosis 3.

Examination Technique

To properly identify clue cells:

• Collect vaginal secretions using a cotton swab
• Place the sample in a tube with 1 mL of normal saline or directly smear on a glass slide with a drop of saline
• Examine under microscope at low and high-dry power
• True clue cells will be visible in the saline preparation 3

Clinical Relevance

Bacterial vaginosis has significant clinical implications:

• Most prevalent cause of vaginal discharge or malodor, though approximately 50% of women with BV are asymptomatic 3
• Associated with adverse pregnancy outcomes including:
  • Preterm delivery (RR 1.4-6.9)
  • Preterm premature rupture of membranes (RR 2.0-7.3)
  • Spontaneous abortion (RR 1.3-2.0)
  • Preterm labor (RR 2.0-2.6) 3
• Increased risk of acquiring sexually transmitted infections 4

Important Distinctions

Recent research has identified important nuances about clue cells:

• True clue cells (with direct bacterial adherence to epithelial cells) are observed in only about 56% of bacterial vaginosis cases 2
• In the remaining cases, epithelial cells may be mechanically entrapped in bacterial masses, forming "pseudo clue cells" 2
• This distinction suggests bacterial vaginosis may represent at least two different conditions: biofilm vaginosis and bacterial excess vaginosis 2

Treatment Implications

When clue cells are identified, treatment is recommended:

• For non-pregnant women with symptomatic BV:

  • Metronidazole 500mg orally twice daily for 7 days (cure rate ~95%)
  • Metronidazole gel 0.75% intravaginally once daily for 5 days
  • Clindamycin cream 2% intravaginally at bedtime for 7 days 4
  • Tinidazole 2g once daily for 2 days or 1g once daily for 5 days 5

• For pregnant women with BV:

  • First trimester: clindamycin cream
  • Second and third trimesters: metronidazole (oral or gel) or clindamycin cream 4

Pitfalls and Caveats

When evaluating for clue cells, be aware of:

• Wet mount can miss trichomoniasis 30-50% of the time, so consider additional testing if suspected 3
• Clue cells should be distinguished from normal epithelial cells with adherent lactobacilli (which have distinct cell borders)
• The proportion of women with true clue cells (versus pseudo clue cells) varies widely across different clinical settings 2
• Bacterial morphotype scoring systems that evaluate the ratio of small bacterial morphotypes to lactobacillary morphotypes may provide more accurate diagnosis than relying on clue cells alone 6

In summary, the identification of clue cells on wet prep is a valuable diagnostic tool for bacterial vaginosis, a condition with significant implications for women's health, particularly during pregnancy.