Endometrial biopsy uses endometrial tissue to determine if there are abnormalities such as inflammation, hyperplasia, or cancer. When the pathology report suggests "insufficient sampling", it does not mean that "no problem was found", but that the amount of tissue obtained is too small for the doctor to make a definitive diagnosis.

Common reasons for undersampling include:

Physiological factors: postmenopausal endometrial atrophy and thinning, sampling tools can only collect a small amount of atrophic tissue;

Anatomical factors: cervical stenosis, intrauterine fibroids distort the shape of the uterine cavity, making it difficult for sampling tools to obtain sufficient tissue smoothly;

Operational factors: Insufficient sampling depth or range to obtain diagnostic-valuable tissue.

In the study of 80,761 Danish women, 17.3% (13,964) had undersampling of initial biopsies, and this percentage increased significantly with age. Only 6.8% of women aged 40-49 are as high as 35.1%, and problems such as endometrial atrophy and cervical stenosis are more common in older women.

The study followed all participants for 4 years, focusing on comparing the incidence of endometrial cancer in the "undersampled" and "normal biopsy" populations, and came to two core conclusions:

During the follow-up period, 368 people in the undersampling group were diagnosed with endometrial cancer, with an incidence rate of 2.6%; while only 423 people in the normal biopsy group were diagnosed, with an incidence rate of only 0.7%. Excluding age, the risk of cancer in undersampled individuals was 3.7 times higher than that of the normal population (HR = 3.7, 95% CI 3.56 to 3.84), a statistically significant difference.

This suggests that insufficient sampling may not be "simply not taking enough tissue", but may be that the cancer lesion is not covered by the sampling, such as the location of the lesion is hidden, or the sampling tool is not touched, resulting in the initial biopsy missed.

Further analysis found that age was an important "interfering factor": the risk of endometrial cancer increased significantly with age (0.8% for 40-49 years old and 11.3% for 60-69 years old), while older women accounted for a higher proportion of undersampled people.

When the statistical model adjusted for age, the risk of cancer in undersampled people was only 16% higher than in the normal population (HR=1.16, 95% CI 1.02-1.31). This shows that the high risk of undersampling is partly caused by "age" itself, not directly caused by insufficient sampling, but even if the influence of age is excluded, the risk is still slightly higher than that of normal people and cannot be completely ignored.

The study not only reveals the risks, but also provides practical guidance for clinical treatment, especially for the question of "whether to need to be reviewed" that patients and doctors are most concerned about

The study found that 56.1% (7834 people) of those with insufficient sampling did not undergo follow-up biopsies, although Danish guidelines recommended repeat testing for this population. Although the study speculates that "the probability of missed cancer is extremely low among those who do not re-examine" (if cancer exists, symptoms will often appear within 4 years and seek medical attention again), it still suggests that some high-risk groups may miss the opportunity for early diagnosis due to non-re-examination.

Young people (<50 years old): If the sampling is insufficient and there is no continuous bleeding, and the endometrium is thin (<5mm) on ultrasound, it can be observed for a short period of time under the guidance of a doctor, and there is no need to force repeat biopsy.

Elderly people (≥50 years old): Due to the high risk of cancer, the risk is still slightly higher even after age adjustment, it is recommended to give priority to repeat biopsy (such as hysteroscopically guided sampling to improve accuracy), or evaluate the thickness of the endometrium through transvaginal ultrasound, if the thickness is > 5mm, further examination is required; If the thickness is < 5mm and there are no bleeding symptoms, caution can be observed.

For example, in people over 60 years of age, if ultrasound suggests thickening of the endometrium, repeat biopsy can detect about 10% of occult cancers (data from similar studies in Canada), avoiding missed diagnosis.

Regardless of the initial biopsy results, you should contact your doctor promptly if you experience the following symptoms:

1. Re-bleeding after menopause (even if the amount is small);

2. Abnormal vaginal discharge (such as purulent, bloody);

3. Lower abdominal pain or pelvic discomfort continues to worsen.

Despite the large sample size and authoritative data of this study, there are still three points to note:

Lack of clinical details: information such as the patient's weight, endometrial thickness, and whether hormone replacement therapy is used is not collected, which may further affect cancer risk judgment;

The definition of insufficient sampling is not uniform: "whether the tissue volume is sufficient" depends on the subjective judgment of pathologists, and the standards of different doctors may be different, which may lead to bias in the classification of some cases.

Biopsy type not distinguished: It is impossible to determine whether undersampling is caused by "blind biopsy" or "hysteroscopically guided biopsy", which is usually more accurate and has a lower missed diagnosis rate.

The AJOG study uses real data from more than 80,000 people to tell us that those with insufficient endometrial biopsy sampling do have a higher risk of endometrial cancer than those with normal biopsies, but this risk is largely related to "age" ； After adjusting for age, the risk increased only slightly by 16%.

For patients, there is no need to be overly anxious about "insufficient sampling", but it should not be taken lightly, especially for people over 50 years old and with persistent bleeding symptoms, they should take the initiative to communicate with their doctors about the review plan; For doctors, it is necessary to combine age, ultrasound results, etc., to avoid "one-size-fits-all" review or observation, and minimize the risk of missed diagnosis while reducing excessive medical treatment.

In the future, with the unification of the pathological criteria of "insufficient sampling" and the inclusion of more clinical factors (such as body weight and hormone levels), the management of such populations will be more accurate, providing stronger support for the early prevention and control of endometrial cancer.

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