Gynecor™ is the lab that provides the test kits and processes the ECC/ ECB and biopsy specimens for the TruTest™ endometrial biopsy and Resolve™ Comprehensive Colposcopy. Only Gynecor™ offers this ground breaking method which takes advantage of both histology and cytology examinations for a more complete picture of the patients’ health.

Cytology and histology samples are simultaneously collected, insufficient sampling is minimized and among successful collections, we have cytology material to examine 100% of the time. Gynecor’s™ fixative preserves the three dimensional structure of cell aggregates, therefore similar criteria that are used for histology pattern diagnoses are applied to cytology “microbiopsy” diagnoses. When both histology and cytology are available, complementary information from both affords greater reliance on the final diagnosis. In addition, Gynecor™ delivers rapid results within 72 hours (3 working days) of the specimen being received in our laboratory. All reports can be accessed online at no additional charge through Webdox, and images are posted on abnormal (malignant and premalignant) diagnoses. Clients may call any of Gynecor’s™ expert pathologists for physician-to-physician consultations, and kits and UPS shipping are provided at no charge.

Gynecor’s™ “all purpose” cell and tissue fixative preserves cells, cell aggregates and small tissue fragments, allowing the same criteria that are generally used for histology pattern diagnoses to be applied to cytology diagnoses. Our proprietary fixative, blended by Gynecor™ under GMP conditions, allows fixation and dispersion of the entire sample once it has been collected (allowing for the creation of “representative” cytology and histology slides). It does not distort the architecture of the endometrial glands, endocervical glands, or cervical squamous mucosa.

Yes, the fixative allows Gynecor™ the capability to analyze both the histology and cytology components of the specimen. It also removes up to 0.25 ml (about 5 hanging drops) of blood per 15 mL vial. You can also use it for any and all biopsies done in the physician’s office (including LEEPs and small conization specimens) that then can be sent to Gynecor™ for processing. If you spill the fixative, do not use a different one. Instead, open another Gynecor™ kit and use one of its vials. Your Gynecor™ Pathology Sales Representative can provide your practice with extra vials at no charge. We can accept LEEPs and Cones returned to us in formaline vials, however, we will able to report on histology only.

Gynecor™ accepts all insurance plans (with a discount provided for self pay patients when requested). Because the brush collection portion must be returned to Gynecor™ for both cytology and histology testing, the testing kits for the Resolve™ Comprehensive Colposcopy and the TruTest™ endometrial biopsy, as well as the UPS shipping labels to return them to the lab, are all provided at no charge to the physician.

Both Gynecor’s™ Resolve™ and TruTest™ kits are made up of brushes and fixative. The two cytobrushes along with the fixative do not require 510K because they are Class I devices. TruTest's™ Tao brush is a Class II device which is FDA approved. The liquid-based method is an anatomical pathology process, which is not FDA regulated (so it cannot be FDA approved). The automated machine is considered a device and therefore requires FDA approval, while Gynecor’s™ method is manual so it does not. All components of Gynecor’s™ kits are compliant with FDA regulations and, as stressed above, manual processing does not require FDA approval.

Endometrial Intraepithelial Neoplasia, (EIN) is a clonal neoplastic premalignant lesion of the uterine lining that predisposes to endometrioid endometrial adenocarcinoma. It is composed of a collection of abnormal endometrial cells, arising from the glands that line the uterus, which have a tendency, over time, to progress to the most common form of uterine cancer—endometrial adenocarcinoma, endometrioid type.
Source: Wikipedia

Referring to Dr. John Maksem’s paper on ECC vs. ECB, often the brush was the only means by which endocervical adenocarcinoma in situ or glandular involvement by a high grade squamous intraepithelial lesion was detected. There are actually two cytobrushes in each Gynecor kit, both to be used and returned in the same vial of fixative. The first brush is meant to clear excess mucus from the endocervical canal. The second brush is meant to be used vigorously with a watch-winding motion in order to obtain epithelium and tissue microbiopsies from the endocervical canal.

There are many, starting with our standards: cytology and cell block histology (not for pap tests except in very unusual cases). Others currently include:

• HPV typing by PCR
• Chlamydia testing by PCR
• N. gonorrhea testing by PCR
• Herpes Simplex Virus detection and typing by PCR
• Genetic screening for Cystic Fibrosis (common mutations) by PCR
• Genetic screening for thrombophilia conditions by molecular methods

Tests for HPV, chlamydia and gonorrhea are run off of the cytobrushes provided in both the TruTest™ and Resolve™ kits for ECB collection from the cervix. In general, colposcopies are performed much more frequently than endometrial biopsies, but either one can provide an STD result when ordered.

It is generally accepted that the preferred treatment of a low grade lesion is watchful waiting and follow up. Thus, colposcopies are used to find high grade disease with the entire cervix treated in positive cases. Therefore, there is no need to map the biopsy sites and go through the time consuming process of labeling each one in a separate vial. It makes more sense to optimize collection and processing conditions to detect high grade disease; and, this is done by combining cytology and histology results, instead of depending on histology alone to identify a high grade epithelial lesion.

Histology depends on having enough tissue to yield an accurate test result. However, a tissue specimen is sometimes hard to collect, especially in post-menopausal patients.. Gynecor™ fixative is multifunctional and can be used for both histology and cytology. Therefore, what is lost to one mode of examination may be detected by the other. For example, cytology outcomes may be available when histology results are not. Unlike other tests that may obtain insufficient tissue sampling, Gynecor's™ test results are not limited to histology only so they are successful more often with whatever specimen is collected.

No. Unlike other labs, Gynecor uses cytology synergistically with histology. Each method may provide information that the other may not. While there may be redundancy, since the two methods provide much of the same information, we cannot know before hand which samples will provide only duplicate information, which will provide truly synergistic information, and in which cases one method will “salvage” the case by providing the only useful information. The redundancy provides a quality confirmation of the findings.

Cytologies are very important because they add about 20% more information than is obtained with just the histology. Using this method, Gynecor™ has been able to diagnose ovarian carcinoma in transit, endometrial intraepithelial neoplasia and endometrial intraepithelial carcinoma. We believe that it would be a great disservice to the patient to not do a cytology on all of the vials that we receive for testing. Since our fixative allows us to do this and to frequently correlate the results with the histology, we get a much more reliable result.

There are many, starting with our standards: cytology and cell block histology (not for pap tests except in very unusual cases). Others currently include:

• HPV typing by PCR
• Chlamydia testing by PCR
• N. gonorrhea testing by PCR
• Herpes Simplex Virus detection and typing by PCR
• Genetic screening for Cystic Fibrosis (common mutations) by PCR
• Genetic screening for thrombophilia conditions by molecular methods

If you know the HPV genotype to start with, and then the patient has an HPV related lesion on follow up one can:

1. Determine that it is a new infection (which is good, because it carries with it a high likelihood of regression) or
2. Surmise that it is a persisting or integrated infection (which is bad, because it carries with it a higher likelihood of progression). Persisting infections accompanied by cytological atypia are more likely to eventuate in high grade lesions than are new infections; and this may effect the woman’s therapeutic options.

Since the patient has been recommended for colposcopy or biopsy, it is likely that HPV test came back positive at time of Pap. Even if it came back negative, there is a small but substantive failure rate of HPV tests done at time of Pap, (about 12%). The General Triage Protocol recommends that patients be retested in this case, (a minimum of annually at first and then every three years afterward). Besides that, the standard test commonly run at time of Pap may only detect the virus, (and possibly assign it into a high risk category). The Resolve Colposcopy and TruTest endometrial biopsy identifies HPV genotype for the exact type of HPV virus present. Since there are dozens of high risk types of HPV genotypes, it becomes important to track the virus history to see if the woman is clearing the infection, if she is becoming re-infected, or if the infection is persisting and possibly becoming integrated. If the same HPV type is recurring, then it is likely that the virus has integrated into the woman’s DNA. This would be a state whereby any atypical lesion would have a greater chance of persistence or progression rather than spontaneous resolution. Thus, the Resolve HPV test offers PCR based genotyping, which gives the doctor important information that could be used at the time of patient follow up in determining appropriate treatment options for that woman.

ASC-US stands for Atypical Squamous Cells – Undetermined Significance. It can represent:

1. HPV disease without enough features to be morphologically definitive, or
2. Reactive changes that are not HPV related, or
3. A sample where there are abnormal cells but so few that we cannot hazard a definitive diagnosis.

We do not always suggest HPV testing for cases that we report as ASCUS or AGC. In some instances, it is apparent from the ICD9 codes, history, or other case findings that HPV (at least HR status) is already known. With Pap tests, we will be doing this testing reflexively (if enabled by the clinician), so no suggestions would be necessary.

A negative HPV result on an ASC-US sample indicates that one of two possibilities pertains:

1. HPV related disease is in fact not present and the ‘Atypical Squamous Cells’ are benign reactive changes that were (albeit unavoidably) overcalled by the lab, or
2. There were not enough viral DNA copies present in the residual sample analyzed for HPV to give a positive result (false negative due to sampling problem) i.e. the sample is deficient both in diagnostic cells and viral DNA.

No. We are required to submit all reports, regardless if the patient’s results are high risk or not. It is important for the physician to know if a previous infection has cleared or a new one is starting up.

The TruTest™ performs cervical brushings and endometrial biopsies to examine both histology and cytology, which are collected simultaneously using the TruTest™ endometrial brush method of sampling. The testing kit provided by Gynecor™ has one TruTest™ endometrial brush (used for the collection of endometrial tissue), and two cytobrushes (one is used to ‘clean’ mucus and debris from the cervix and the second is used for enhanced cell and tissue collection from the squamo-columnar junction of the uterine cervix).

The TruTest™ endometrial brush is an FDA approved, Class II device used to obtain endometrial cell samples. The TruTest™ method of sampling is a process of obtaining endometrial tissue, via the TruTest™ endometrial brush and squamo-columnar junction cervical tissue via the cytobrushes. The TruTest™ endometrial brush head is 3.0 cm in length and samples the endometrium to a depth of 1.5 to 2 mm. Using this brush, a simple watch-winding motion collects endometrial cells and tissue in a quick and generally painless fashion, and yields excellent diagnostic outcomes.

The TruTest™ endometrial brush samples a substantial portion of the endometrial surface’s lining. This can save a woman from undergoing a traditional endometrial biopsy, which is generally a more painful procedure. The TruTest™ endometrial brush affords a better tolerated invasive collection of endometrial tissue. When used correctly, it minimizes sample contamination from the endocervix and vagina, thus reducing a source of diagnostic error by confining sampling to the endometrial cavity (resheathing the brush before it is withdrawn from the uterine cavity is a critical step that protects and retains tissue during brush withdrawal).

With the TruTest™, the operator gets a specimen more than 95% of the time, as compared to about 80% of the time with other samplers like the Pipelle. The TruTest™ endometrial brush is designed to achieve global sampling of the endometrial surface while causing less pain for the patient. Studies show that it may have greater sensitivity than pipelle: “A study conducted in 101 women compared two endometrial biopsy techniques, Tao Brush and Pipelle, using both techniques during the same office visit. Sensitivity for Tao Brush was 95.5 percent, and 86 percent for Pipelle's. Both have specificities and positive predictive values of 100 percent and negative predictive values of 98 percent.“
Source: National Cancer Institute

Although the TruTest™ endometrial brush is intended for the early detection of endometrial carcinoma and its precursors, it can be used to monitor the endometrial condition of patients receiving estrogen replacement therapy or tamoxifen. It is also useful for the procurement of uncontaminated endometrial samples for microbiologic studies from patients with suspected endometritis. It has the potential to be used for endometrial dating for patients with infertility disorders. In our clinical trials and sampling tests using hysterectomy specimens, adequate and representative endometrial samples without contamination from endocervix and vagina were consistently obtained by this device.

Yes. The best time to test for this is postovulatory day 7-10, which corresponds to days 21-24 of a referent 28 day cycle.

The sampling is limited to mucosal lesions that are represented in the upper 2 mm of the endometrium, but, as for cancer detection, these conditions are satisfied more than 97% of the time for all uterine cancers and more than 99% of the time for adenocarcinomas of endometrial origin.

From among approximately 1650 consecutive brushings that we reviewed, Gynecor™ reported out about 20 polyps. As with other office biopsy samplers, polyp acquisition is a serendipitous event. Hysteroscopy and snare biopsy or formal dilation and curettage remain the preferred ways of identifying and collecting polyps, especially large, symptomatic ones.

Yes. This condition may represent a variety of changes such as blood or inflammatory cells and sometimes serous fluid in the uterus. This is usually due to cervical canal obstruction. In such cases, the retained fluid should be drained and the uterine wall lining sampled at a second setting after the uterine walls once more oppose each other (no matter what collection device is used).

If the cervix is stenotic it must be dilated, regardless of the collection device used. Generally, we advise sounding the uterus before any collection procedure. If the sound passes easily, the brush generally does also.

About the upper 2 mm will be sampled. Most pathological conditions of the endometrium express themselves at the surface (stromal sarcomas are notable exceptions).

A benign abnormality simply means it is not cancer or endometrial precancer, but either: (1) a change which has a mild to moderate association with cancer or endometrial precancer such as benign, unopposed estrogenic states; (2) a change which is not normal cycling endometrium or atrophy, and which may explain why a woman is experiencing symptoms such as abnormal vaginal bleeding; or, (3) a change which indicates that further workup is necessary.

My feeling is that unless the gel is almost completely cleared out of the way of the cervical os, it would likely contaminate the collection and affect the quality of the cytology specimen.

In such a situation, it would be better to use two brushes and fix them in one vial.

Bleeding is an indication for endometrial biopsy so this is a common occurance. Clinicians will try to alleviate patients' bleeding symptoms with medication even before biopsy and that’s generally OK (although it would be helpful for us to know when and what medication was actually taken byt he patient prior to biopsy). We have seen many examples of adequate tissue and cytology during menstrual phase, even with menorrhagia. Unlike the Pipelle, which scrapes the endometrium and draws the blood into the sample, the proper use of the Tao brush tends to entrap tissue in the bristles, and then re-sheathing before removal helps by wringing out the blood to some extent, thus giving us a better tissue to blood ratio. Also, remember that Gynecor's unique fixative allows us to deliver a result on cytology from every specimen returned to us, regardless of what the tissue yields.

While there are no reports of complications, theoretically the brush could entangle in the IUD, and it would be prudent to inform the patient of this occurrence. It is recommended that an endometrial biopsy is performed prior to the insertion of an IUD.

We do not currently offer microbiology testing as there is no data describing the reliability of culture results from this method. (The Tao® Brush is provided in a sterile pack. If, after obtaining the endometrial sample, the physician were to retract the sheath and inoculate a tube of sterile broth transport media with the brush and its content sample, then that tube could be submitted for culture and sensitivity.)

Placing the bead of the brush of the fundus is the best method for collecting samples. Endocervical contamination is a problem and adherence to proper technique is needed to keep it at a minimum. Inserting the brush all the way to the fundus before retracting the sheath is part of that technique. Clearing the endocervical mucus with a cervix brush prior to using the Tao brush is another. Replacing the sheath before removing the brush through the endocervical canal is a necessary third measure. The 3.5 cm length of the brush (bristle portion) is sufficient to sample the average endometrial cavity. If the uterine cavity is known to be a good deal larger than average, then two brushes can be used. Brushing the lower uterus would only increase endocervical contamination without increasing the yield of endometrium. We seldom lack lower uterine segment representation in our samples, even without specially targeting the area, another indication that the length of the brush is generally sufficient. In fact, the far more common problem with samples is too much sampling of the LUS and not the rest of the endometrial cavity.

1. Grading of endometrial carcinomas is essentially the same as with Pipelle® with the same provisos, i.e., it is based on a sample that is not the entire endometrium. (Any office biopsy and even dilatation and curettage are the same in this respect.) Subsequently, there may be undercalls compared with the hysterectomy diagnosis due to sampling, and there may also be overcalls because a high grade, but superficial and focal change, was removed by the biopsy sample but not included in the sampling of the hysterectomy specimen.
2. Grading of type 1 carcinomas of endometrium in histopathology is based on percentage of solid growth pattern exclusive of squamous metaplasia. Solid growth may sometimes be seen in brush biopsy samples but we tend to rely more on cytological features. Principally (but not exclusively), the presence of grade 3 nuclear changes will up-grade an architectural type 1 grade 1 to a grade 2. The type 1 grade 3 should show discernable solid growth (unless bad luck would have it that we sampled only the 10% non-solid growth area of a grade 3 lesion) and high grade nuclear changes.
3. Histologically, there is no advantage [nor any serious disadvantage] of the Tao® brush over Pipelle®. The very important points however are two:
   • The Tao brush causes less pain to patients for comparable histological information (except for polyps, where the Pipelle® does have an acknowledged edge)
   • Cytology can, and absolutely should, be used together with histology when evaluating Tao brush samples and the synergy of methods provides better performance, especially (but not exclusively) in the post-menopausal population where endometrium is sparse. No one does this with Pipelle® (although with our fixative, they could – labs just don’t bother to go to the extra trouble to obtain the cytological information from their samples to help their patients)

ACOG has taken no formal position on endometrial cytology. According to the FDA however, the TruTest brush is a non-cervicovaginal cytology test. By convention, all non-cervicovaginal cytology tests in which sufficient material presents itself for cell block analysis should have cell blocks.

Endometrial cancer is the most common female genital tract malignancy and more than 42,000 cases are diagnosed each year. One in 142 women will be diagnosed with cancer of the cervix uteri during their lifetime. Endometrial cancer is the fourth most common in women (behind lung, breast and colon) and an estimated 7,400 deaths are expected in 2007 (twice as many as cervical cancer).

Excessive estrogen that is unopposed by a progestin has historically been associated with an increased risk of endometrial cancer. Interestingly, women taking combination birth control pills (estrogen + progestin) or those with intrauterine contraceptive devices (whether they contain a progestin or not) have a lower risk for endometrial cancer. Higher risk factors are seen among woman who do not ovulate regularly, who began menstruating before age 12, who have never been pregnant, have a history of infertility, are 50 or more pounds overweight, have conditions associated with unopposed estrogen such as endometrial hyperplasia, or have late onset of menopause (around age 51). Often overlooked are certain cancer family syndromes, notably the Lynch non-polyposis colon cancer syndrome (in either male or female family members), carries with it a substantial risk of endometrial cancer. Women with the Lynch syndrome are almost guaranteed to get endometrial cancer if they live into their eighties. Women put on hormone replacement therapy, such as breast cancer patients taking tamoxifen, are at an increased risk of developing cancer as well.

Currently, there is no standard screening test for endometrial cancer. In fact, routine screening is not recommended due to the lack of an appropriate, cost-effective and acceptable test that reduces mortality. The Tao brush™ was initially proposed by Dr. Tao as a remedy to this situation. Systematic surgical staging, surgery, radiation therapy, progestin therapy or chemotherapy have all played a role in patient treatment for this disease.