What Is a Clue Cell and What Does It Indicate?

A clue cell is a specialized finding observed during the microscopic examination of vaginal fluid. It is not a distinct type of human cell but an exfoliated vaginal epithelial cell heavily coated with bacteria. The presence of these altered cells indicates an underlying change and imbalance in the natural vaginal microenvironment.

What Makes a Clue Cell Distinct

A clue cell earns its name because its appearance offers a clear microscopic “clue” to a specific diagnosis. Under a microscope, the cell’s surface appears stippled or granular due to the dense layer of microorganisms adhering to it. This bacterial coating is so extensive that it obscures the distinct, sharply defined borders characteristic of a normal, healthy vaginal epithelial cell.

The primary organism responsible is often Gardnerella vaginalis, though other anaerobic bacteria are also involved. These bacteria bind to the surface of the epithelial cell, blurring the cell margins and making the interior look fuzzy or indistinct. This unique morphology differentiates the clue cell from other cells found in vaginal discharge.

The Condition Diagnosed by Clue Cells

The observation of clue cells confirms the diagnosis of Bacterial Vaginosis (BV), which is the most common cause of abnormal vaginal discharge in women of reproductive age. BV is not considered a traditional infection but rather a polymicrobial syndrome marked by a profound shift in the vaginal microbiome. This shift involves a significant decrease in the protective, hydrogen peroxide-producing Lactobacillus species, which normally maintain an acidic environment.

The decreased presence of Lactobacillus allows for the overgrowth of various anaerobic and facultative bacteria, including Gardnerella vaginalis and Mobiluncus species. This microbial shift results in an elevated vaginal pH, typically rising above the normal acidic range of \(3.5\) to \(4.5\). The main symptom of BV is often a thin, gray or off-white, homogeneous discharge that may coat the vaginal walls.

A characteristic malodor, often described as “fishy,” results from the volatile amines produced by the anaerobic bacteria as they metabolize proteins. Risk factors associated with BV include having multiple or new sexual partners, douching, and a natural lack of Lactobacillus. Untreated BV can increase the risk for serious reproductive health issues, such as pelvic inflammatory disease or complications during pregnancy.

How Clue Cells Are Identified

Clue cells are typically identified using a rapid, in-office test known as a “wet mount” preparation. This procedure involves collecting a small sample of vaginal discharge and mixing it with a drop of normal saline on a glass slide. The specimen is then immediately examined under a light microscope to assess the cellular components and bacteria.

The gold standard for a clinical BV diagnosis often involves the Amsel Criteria, which requires the presence of at least three of four specific clinical signs. These criteria are:

  • Homogenous discharge.
  • Vaginal pH above 4.5.
  • A positive “whiff test,” where a fishy odor is detected after adding potassium hydroxide.
  • Clue cells constituting more than 20% of the total epithelial cells seen in the microscopic field.

An alternative, more standardized laboratory method for diagnosing BV is the Nugent Scoring System, which involves staining the vaginal smear with Gram stain. This system uses a numerical score based on the relative numbers of three bacterial morphotypes: large Gram-positive rods (Lactobacillus), small Gram-variable rods (Gardnerella), and curved Gram-variable rods (Mobiluncus). The simple visual confirmation of clue cells via the Amsel criteria remains a widely used method in clinical settings.

Treating the Associated Condition

Once the presence of clue cells confirms a diagnosis of Bacterial Vaginosis, treatment focuses on restoring the balance of the vaginal flora by eliminating the overgrowing anaerobic bacteria. The first-line therapeutic agents are antibiotics, primarily metronidazole and clindamycin. These medications can be administered either orally or topically as a vaginal gel or cream.

A common regimen for metronidazole is \(500\) mg taken by mouth twice a day for seven days. Topical treatments, such as metronidazole gel or clindamycin cream, are applied intravaginally for five to seven days and are associated with fewer systemic side effects. Patients must complete the full course of therapy to maximize successful eradication. Recurrence is common, with a significant percentage of individuals experiencing a return of symptoms within one year.