Articles - Cancer and Pelvic MassesBy Date of Release Topic January 30, 2000 Carcinoma In situ of the Cervix and What to Expect July 4, 1999 What Does a Positive Fecal Occult Blood Test Mean? April 4, 1999 Screening for Cancer of the Colon or Rectum March 14, 1999 How to tell if an Ovarian Mass is Malignant? February 14, 1999 Laparoscopic Diagnosis of Pelvic Masses - Is it Safe? January 31, 1999 Vulvar Intraepithelial Neoplasia (VIN) and Cancer November 15, 1998 Family History Important for Ovarian Cancer Risk August 16, 1998 Hereditary Ovarian Cancer Reduced by Oral Contraceptives August 2, 1998 Atypical Glandular Cells of Unknown Significance (AGCUS) April 26, 1998 Risk of False Alarm for Breast Cancer February 22, 1998 Saline Infusion Sonography Diagnosis of Bleeding December 21, 1997 PAP Smear Diagnosis of Endometrial Cancer December 7, 1997 Plant Estrogens and Breast Cancer November 9, 1997 Vulvar Cancer and Human Papilloma Virus (HPV) October 10, 1997 PAP Smear Recommendations
What Does a Positive Fecal Occult Blood Test Mean?
Frederick R. Jelovsek MD
When the doctor does a rectal exam and smears a stool sample on a card to test for blood in the stool, or gives you a paper to drop into the toilet to look for a color change, this is known as testing for occult gastrointestinal bleeding. Occult means you do not know there is blood in the stool, i.e., you cannot see bright red recognizable blood like you might see if you had bleeding from hemorrhoids. Testing for fecal occult blood is commonly used as a cancer screen for colon cancer. A positive test can mean other conditions however. A review article, Rockey DC: Occult gastrointestinal bleeding. N Engl J Med 1999;341:38-46 addresses some questions you might have if you turned out to have a positive test.How much bleeding in the gastrointestinal tract is needed to turn a test positive?
There are two answers to this question. It depends upon which specific chemical method is used to detect the blood and also where in the gastrointestinal (GI) tract the bleeding occurs.
The most commonly used method is the guaiac-based fecal occult blood test. It usually picks up about a daily blood loss of about 10 ml (about two teaspoonfuls). Normally, there is only about 0.5 to 1.5 ml of blood a day that escapes blood vessels into the stool each day. There are more sensitive tests than the guiac such as a heme-porphyrin test or a immunochemical test, but the former test is not used much due to the high false positive rate. The latter test is very sensitive -- it picks up as little as 0.3 ml -- but it needs to be processed in a laboratory so it is much less likely to be used as a screening test. It does not detect blood from from the stomach and upper small intestine so it is much more specific for bleeding from the colon or lower gastrointestinal tract.
The guiac-based test will turn positive from bleeding anywhere in the GI tract but it will also turn positive if you have had a recent meal of red meat. Other dietary factors and even stool transit time can affect the test outcome.
What are some of the causes other than colon cancer that can show a positive fecal occult blood test?
Any process that causes an increased amount of bleeding in the GI tract will turn the test positive. This could be a cancer, but it also could come from an ulcer, bacterial infection, blood vessel malformation, parasite infections or even nosebleeds. The differential diagnosis is:
Differential Diagnosis of Occult Gastrointestinal BleedingMass lesions
- carcinoma of any site
- large (more than 1.5 cm) adenomatous polyp
- erosive esophagitis
- ulcer of any site
- linear cuts in a hiatus hernia
- erosive gastritis
- celiac disease
- ulcerative colitis
- Crohn's disease (regional enteritis)
- nonspecific colitis
- unexplained cecal ulcer
- vascular ectasia (blood vessel inflammation)
- liver vein hypertension
- gastrointestinal varicose veins (varices)
- other blood vessel abnormalities
- tuberculous enterocolitis
- coughing blood from lungs and swallowing it
- nosebleeds and mouth cavity bleeding
- long distance running
- falsified causes
I have heard iron supplementation and sometimes aspirin can cause a false positive test. Is that true?
Many people believe that oral iron medications cause a false positive fecal blood test. They really do not. The only problem is that it may confuse someone in reading the test because the dark green or black appearance of iron in the stool may may be mistaken for the blue color typical of a positive guiac test.
Another misconception is that aspirin or anticoagulants often cause GI tract bleeding. While it is possible that this happens on some occasions, it is actually infrequent, i.e., most patients on anticoagulants or aspirin do not have guiac detectable fecal blood levels. Some studies of patients on anticoagulants who had positive fecal occult blood tests show over 90% causes from major gastrointestinal conditions rather than just due to the anticoagulants.
There are occasionally other causes of false positive fecal occult blood tests that are from ingested substances. Any hemoglobin/blood in red meat can affect the test as well as some vegetable enzymes on occasion
Is there a relationship between iron deficiency anemia and gastrointestinal bleeding?
Iron deficiency anemia is usually diagnosed by a hemoglobin value of less than 12 g/dl and a serum ferritin level of less than 45 ug/l. In the U.S., 5-11% of women have iron deficiency anemia, often on a basis of menstrual bleeding problems. However, chronic occult gastrointestinal bleeding is also a frequent cause of iron deficiency. Anytime a woman is diagnosed with anemia and it turns out to be of the iron deficient form, an investigation should be made to make sure the blood loss is not from somewhere other than menses. At a minimum, a test for fecal occult blood should be performed. As much as 12% of iron deficiency anemia in premenopausal women may be due to serious gastrointestinal anomalies.
What happens if they can't find the cause for a positive fecal occult blood test?
When the work up to evaluate occult fecal blood is completed (see colon cancer screening article below), about 5% of patients with gastrointestinal bleeding will not have a source for their bleeding found. In this case some additional studies may be needed and sometimes "oscopy" studies may need to be repeated with different or more experienced gastorenteroscopists.
A radioactive technetium-99m scan may be performed which can detect as small a blood loss as 0.1 ml per minute. It is useful only to confirm that there is GI bleeding and where in the GI tract,in general, the bleeding is occurring. It still does not diagnose the cause. Enteroscopy is another study that may be used to look at the small intestine which cannot be seen with gastroscopy (looking in the stomach) and colonoscopy (looking up the colon).
Sometimes even after all these studies, a source of the bleeding may be found. When that happens the best that can be done is just to have close follow up and occasionally repeat any of the studies as indicated by symptoms.
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Screening for Cancer of the Colon or Rectum
Frederick R. Jelovsek MD
Colorectal cancer is a leading cause of cancer deaths and the most common gastrointestinal malignancy. The lifetime risk of colon and rectal cancer is 6-7% and it increases sharply after age 50. Many women are not aware that their chance of getting colorectal cancer is about 5 times greater than of getting ovarian cancer. For someone interested in living a long life, it would be wise to know how to be screened to pick up colorectal cancer in its earliest stages.
In a recent continuing medical education article, Early DS: Colorectal cancer screening: An overview of available methods and current recommendations. South Med J. 1999; 92:258-265, we are presented with a good overview of how to go about screening for this devastating cancer.How does cancer of the colon develop?
The skin lining the colon (mucosa) sometimes undergoes a transition from normal to glandular hyperplasia (adenomatous polyps) to cancerous tissue in a stepwise fashion over a 5-15 year time period. Nearly all colon cancers arise from these adenomatous polyps. The opposite is not true, however, that all polyps develop into cancer. In fact most polyps of the colon do not become cancerous, but their existence is a risk factor. There is one exception to this normal-adenomatous polyp-cancer progression and that is in ulcerative colitis in which the cancers are preceded by a different process, a dysplasia or non-polypoid abnormal growth pattern. Thus in most cases, if adenomatous polyps can be detected and removed, that may help prevent colon cancer.
What different diagnostic tests are available to detect colon or rectal cancer?
The basic tests available to screen for colorectal cancer are flexible sigmoidoscopy, checking the stool for hidden blood (fecal occult blood), dye and air in the colon (air contrast barium enema), and looking beyond the lower part of the colon (sigmoid) into the transverse and ascending colon using a scope called colonoscopy.
Approximately 50-65% of colon cancers occur in the lower part of the colon that is visualized with a flexible sigmoidoscopy. Studies have shown that sigmoidoscopy is associated with a 59-79% reduction in cancer mortality. Checking the stool for blood is considered a cancer test because a polyp would need to be fairly large sized in order to bleed. In other words, looking in the colon will pick up polyps sooner than waiting for them to grow big enough to bleed. Fecal occult blood tests have been shown to reduce colon cancer by about 33%. Air contrast barium enema can pick up more lesions than sigmoidoscopy but is not as good as colonoscopy. If the barium enema is abnormal, a colonoscopy has to be done anyway so this is not as cost effective as a screening test. Colonoscopy is a more sensitive test to find polyps and cancer but it is more expensive and occasionally patients have serious complications (3-17/1000) or even death (2/10000). It is used for screening women who are at high risk or who have a positive fecal occult blood test.
What are the screening tests recommended for a woman at average risk of colon cancer?
Starting at age 50, it is recommended that women have a yearly fecal occult blood screen and a flexible sigmoidoscopy every 5 years or a total colon exam ( barium enema or colonoscopy) every 5-10 years.
What would make a woman at higher than normal risk for colorectal cancer?
If a woman has had a history of having adenomatous polyps or a past colon cancer, a history of inflammatory bowel disease (ulcerative colitis, regional enteritis), or a strong family history of colorectal cancer or adenomatous polyps, then she should be considered at high risk.
Having had a colorectal cancer, there is an increased risk of a second colorectal cancer of about 6% over an 18 year period. Over a third of women in whom colon polyps have been detected and removed have a recurrence of the polyps. If there is a family history of polyposis or colon cancer, there may be a genetic tendency toward colon cancer. This needs to be investigated and sometimes genetic testing will have to be performed even though a genetic tendency only explains about 5% of colorectal cancers.
Should a woman at high risk for colorectal cancer be followed or screened differently than a woman at average risk?
The table below gives Early's recommendations:
Colorectal Cancer Screening in High Risk Individuals
|Risk Factor||Screening Test||Frequency|
|history of colorectal cancer||colonoscopy||every 1-3 years|
|history of adenomatous polyps||colonoscopy||every 3 years|
|history of inflammatory bowel disease||colonoscopy||every 1 to 2 years, after 8-10 years of extensive colitis (right and left) or after 15 years of left sided colitis|
|family history of colorectal cancer or adenomatous polyps|
|first degree relative||fecal occult blood test,
every 3-5 years starting at age 40
|two first degree relatives
(or young age at diagnosis
|fecal occult blood test,
every 3-5 years starting at age 40
or at 10 years younger than the youngest case
|hereditary nonpolyposis colorectal cancer||colonoscopy||at 5 years younger than the youngest case in the family or at age 25, then every 1 to 2 years|
|familial adenomatous polyposis||flexible sigmoidoscopy||at age 12 then yearly|
How to tell if an Ovarian Mass is Malignant?
Frederick R. Jelovsek MD
Just as a breast lump is frightening because it may mean cancer, so is a pelvic mass that the doctor thinks may possibly be ovarian cancer. Most women, if given a choice, would rather have a gynecologic oncologist who has had specialized training do the surgery. This is especially true if they knew that the mass was going to turn out to be malignant and spread beyond the ovary. Most local hospitals do not have a gynecologic cancer specialist on staff, so the dilemma becomes "what criteria should be used to strongly recommend that a woman have her surgery at a regional center?"
A recent study in Norway looked how to predict whether a woman with possible ovarian malignancy should be referred to the regional cancer center. Tingulstad S et al: The risk-of-malignancy index to evaluate potential ovarian cancers in local hospitals. Obstet gynecol 1999;93:448-52.They looked at 365 women from seven local hospitals that were evaluated with a risk scoring system to see if they should be transferred to the central cancer hospital. This study answers several questions about the ultrasound findings, age, menopausal status and CA 125 serum test measurement (an ovarian cancer antigen) and how they can be used to predict the chance of malignancy.
Can the doctor tell if an ovarian tumor is malignant by vaginal ultrasound?
Malignancy of the ovary cannot be diagnosed with any certainty by ultrasound. The best that can be done is to identify characteristics that make it more likely to be malignant or benign. There are many benign pelvic conditions that can appear on ultrasound as worrisome for malignancy. These include: benign epithelial and functional ovarian cysts, hemorrhagic ovarian cysts, endometriosis, dermoid cysts (benign teratomas), ovarian fibroids, uterine fibroids, fimbrial cysts, hydrosalpinges (swollen, fluid-filled faloppian tubes), pelvic abscesses, pelvic adhesions, bowel adhesions and adenomyosis.
How common are ovarian malignancies in younger women?
If you look at the distribution of ages in this study (confined to women over 30), you will see that benign tumors and causes of ovarian masses can occur in all age ranges. Malignancy of the ovary definitely is higher in older women and lower in frequency in the younger ages.
Risk of Malignancy Age Distribution
After menopause, are not most ovarian masses malignant?
Just as there is an increased chance of an ovarian tumor being malignant at older ages, so is the chance after menopause. Benign pelvic/ovarian masses occur with almost equal frequency before and after menopause.
Risk of Malignancy Distribution by Menopause
|Premenopause||175 (60%)||18 (24%)|
|Postmenopause||115 (40%)||57 (76%)|
Does the CA-125 test accurately predict ovarian cancer?
CA-125 is an ovarian cancer antigen test but it is also positive in many cases of benign pelvic and abdominal disease, especially premenopausal. Fibroids, diverticulitis, liver disease, benign ovarian tumors, endometriosis and other nonmalignant sources can cause an elevation in CA-125. Normal values in most labs are 35 u/ml or less and only when the values are over 100 u/ml is there a great concern for malignancy. Benign causes can be associated with levels higher than 100 u/ml while malignancies, especially early Stage I ovarian cancer can be associated with normal or equivocal levels (35-100 u/ml).
Risk of Malignancy Distribution by CA-125 Level
(average of values)
(lowest to highest)
What changes on ultrasound are most worrisome for malignancy?
There have been different ultrasound scoring systems to try to predict malignancy. Anytime the ultrasonographer sees the following characteristics, there may be an increased chance of malignancy beyond just a simple cyst:
- multiloculated cysts (septations within a cystic area)
- solid areas
- bilateral lesions
- ascites (fluid in the pelvic/abdominal cavity)
- evidence suspicious for intraabdominal metastases
Giving a score of one for any of the above findings, the risk of malignancy cases were divided into :
Risk of Malignancy by Ultrasound Findings
|0||79 (27%)||3 (4%)|
|1||112 (39%)||13 (17%)|
|2-5||99 (34%)||59 (79%)|
Note that many (34%) benign masses have more than one characteristic of malignancy.
When does the chance of ovarian cancer increase enough that it is best to have the initial surgical exploration done by a gynecologic cancer surgeon specialist?
The authors in the Risk of Malignancy study used a scoring system by Jacobs (1990) based on the menopausal status (premenopausal = 1, postmenopausal = 3), ultrasound characteristics (zero or one characteristic ultrasound finding = 1, two or more features = 3) and the CA-125 level (actual value). They then multiply these three values together (RMI= M X U X Ca-125). For example, a postmenopausal woman (3) who had two ultrasound characteristics of malignancy (3) and had a CA-125 level of 50 u/ml, would have a risk of malignancy index (RMI) of 3x3x50 =300. In calculating RMIs for all the patients in their study, Tingulstad et al found:
Risk of Malignancy by Ultrasound Findings
(negative predictive value)
(positive predictive value)
In other words, if a cutoff of RMI=300 is used to predict whether there may be a malignancy present, if the RMI is 300 or over, 3 out of 4 times an ovarian malignancy will be present. If it is less than 300 and a woman stays at the local hospital, 8% of the time (1 out of 12 times) an ovarian malignancy will be found. In this study, none of the Stage 2-4 ovarian cancers and none of the Stage 1C ovarian cancers would be performed in the local hospital. These are excellent findings because almost all gynecologic surgeons can do the surgery needed to fully treat Stage 1 A and B (confined to the ovary (s) and not spread) ovarian cancer.
For more information on this subject on the net:
Laparoscopic Diagnosis of Pelvic Masses - Is it Safe?
Frederick R. Jelovsek MD
If a pelvic, vaginal probe ultrasound shows a complex adnexal or ovarian mass and the doctor says exploratory surgery should be done to rule out possible ovarian cancer, is it safe to just have laparoscopic surgery or should a major abdominal incision be performed? This question comes up very often because there is a fear that laparoscopy could spread a cancer if it were present, or lead to a delay of treatment if full surgery could not be performed at that time in that setting. If the woman is at low risk for cancer based on the ultrasound picture of the pelvic mass, studies have shown a very low incidence of unsuspected cancer. The problem is confined to those situations where the ultrasound characteristics are more worrisome for malignancy.
A recent study, Dottino PR, Levine DA, Ripley DL, Cohen CJ: Laparoscopic management of adnexal masses in premenopausal and postmenopausal women. Obstet Gynecol 1999;93:223-228, looked at over 160 patients who underwent laparoscopic evaluation for a pelvic mass on a gynecologic oncologic service at Mount Sinai School of Medicine, New York, New York, between 1992 and 1996. From this, we can find the answers to women's questions that come up when that pelvic or ovarian mass is first found.It seems that laparoscopic diagnosis of an ovarian mass would always be easier on the women than a large abdominal incision. Why is there any question that laparoscopy should not be the primary approach?
Most of the scientific journal articles suggest that adnexal masses suspicious for malignancy are best managed by laparotomy, a full abdominal incision. One concern about the use of laparoscopy includes the failure to diagnose a malignancy. When you just look at the outside of the ovary you can only tell a malignancy if it has spread outside the capsule of the ovary. If it is still inside the ovary it can look like a normal physiologic cyst. If a large incision has been made, the ovary can easily be opened to look internally. That is much more difficult at laparoscopy.
Another concern is that a surgeon is more likely to let tumor cells spill at the time of removal by laparoscopy than when there is a much larger incisional exposure. Finally, there is the fear that surgeons will just look and diagnose by laparoscopy and not perform the needed tumor resection at the time of laparoscopy, thus delaying treatment of the cancer.
The advantages of laparoscopy include decreased postoperative pain, shorter length of stay, quicker recovery time, less adhesion formation, and lower costs.How likely is it for a pelvic mass to be a cancer?
In this series, benign pathology was found in 87% of the patients, malignancy in 13% or 1 out of 8. All of the benign masses were managed (removed) laparoscopically.What happens if it turns out to be a cancer?
If cancer is discovered a larger incision can be made and a full staging procedure and removal of all tumor and lymph nodes can be performed. While the laparoscopic part adds about 30 minutes more to the procedure than going straight to a full incision in the first place, the full procedure only has to be performed 1 in 8 times. The other 7 times, the patient's recovery is significantly shortened.Can the diagnosis be wrong at laparoscopy?
Diagnosis at the time of surgery is made by "frozen section" pathological review. This technique is known not to be perfect and sometimes there is a discrepancy between the immediate pathological review using frozen section and the permanent pathological slide review about 48 hours later. This study had a 3% discrepancy rate between immediate and final pathology report, but that is the same rate found in other series at laparotomy. In other words there is no difference in this rate between laparoscopy and laparotomy.Should my gynecologist do this procedure or do I need to go to a gynecologic oncologist?
It is difficult to answer this question. Most gynecologists feel comfortable treating Stage I disease with removal of the ovaries, uterus and omentum as well as removing pelvic lymph nodes to make sure there is not microscopic spread. They may not be comfortable removing extensive tumor involving bowel and urinary tract. On the other hand, even in this series less than 12% needed this further surgery.
Even if the gynecologist diagnoses malignancy but does not carry out the definitive surgical therapy, it is imperative that the surgery be carried out fairly quickly. It has been shown that delays of a month can have an effect on the curability of the cancer.When should laparoscopy not be used for diagnosis of a possible cancer of the pelvis?
In this series, any patient that had findings suspicious for metastasis or had a mass that extends above the umbilicus (navel) was not included. They had initial full incisions. The series did include cases where ultrasound showed solid components or complex masses.
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Vulvar Intraepithelial Neoplasia (VIN) and Cancer
Frederick R. Jelovsek MD
Vulvar disease and cancer is certainly not as frequent a problem as are abnormal Pap smears or abnormal uterine bleeding and the concern for endometrial cancer. And yet when the doctor says that a biopsy of the vulva is needed to make sure there is not a malignancy or changes that could become malignant, confusion and lack of knowledge are the rule. Vulvar cancer is only 1% of all female cancers and only represents 4% of all gynecologic cancers. Changes can take place in the vulvar skin just like the abnormal Pap smears and the dysplasia that occur on the cervix, albeit they are much more frequent in the cervix than on the vulva. Women are more aware of genital warts, condyloma accuminata, caused by the human papilloma virus (HPV) and the concern that they may be related to development of vulvar cancer in later life.
A recent review article, Chi DS:The diagnosis and management of vulvar cancer. Prim Care Update Ob/Gyns 1999; 6:24-32, has been quite helpful in answering some of the questions that come up when "vulvar biopsy" is mentioned.What is vulvar intraepithelial neoplasia (VIN)?
Vulvar intraepithelial neoplasia is a preinvasive skin lesion of the vulva similar to cervical intraepithelial neoplasia (CIN) or dysplasia, that can occur in the cervix and result in abnormal Pap smears. It is diagnosed on biopsy the same way that CIN is diagnosed, i.e., how extensive the abnormal nuclear changes in the skin are. If only the bottom third of the epithelial (skin) lining has these changes, mild dysplasia or VIN I is diagnosed; if the full thickness of the epithelium has abnormal cells, VIN III, also called vulvar carcinoma in situ, is diagnosed. Just like in the cervix, if these vulvar changes are left untreated for many years, some of them turn into an invasive cancer in later years. Therefore doctors recommend excising that abnormal tissue so as to prevent any cancer from developing.How can I tell if I have any vulvar dysplasia or vulvar cancer?
Chronic vulvar itching and burning or a slightly raised skin lesion are the most frequent findings of this problem. Usually the itching has persisted for years with perhaps multiple treatments with various skin creams. Lesions may be pink, red, white or gray in color. About 25% of lesions are hyperpigmented, appearing darkened like a mole or freckle. These more advanced, but noncancerous changes such as VIN III (carcinoma in situ) or actual cancer tend to occur at older ages. The average age of VIN III is 45-50 years of age while that of invasive vulvar cancer is about 65-70 years of age. As you can see, it takes, on the average, well over a decade for the severe preinvasive stage to go on to cancer if it is going to.What causes vulvar dysplasia (VIN) and cancer -- is HPV involved?
More than one infectious agent has been suspected as the cause of vulvar dysplasia. Herpes simplex virus, granulomatous STD infections, and human papilloma virus have all been shown to be associated. In fact 80%-90% of all VIN has been shown to have HPV DNA present. Interestingly, only 30-50% of invasive vulvar cancers have been shown to have HPV DNA in them. Some experts have postulated that patients with squamous cancers of the vulva can be divided into two groups that may have different causes for their cancers. Younger women (35-55) tend to have cancers associated with HPV infection and VIN. The lesions are usually multifocal over various areas of the vulva. Older women (55-85) have more of a history of vulvar inflammation, itching and burning for many years and lichen sclerosis, a whitening skin change. Their cancers are usually unifocal and do not show evidence of HPV infection or vulvar intraepithelial neoplasia changes in the surrounding tissue.How likely is it for vulvar intraepithelial neoplasia (VIN) to progress to cancer?
Overall, studies have shown that only 4% of women with VIN have gone on to have invasive cancer. You must remember though, that all of these women received treatment for the VIN. In one small study, 7 of 8 women who had VIN III and went untreated, went on to have invasive vulvar cancer. It would seem prudent to treat all VIN lesions but being careful not to mutilate the vulva in the process since VIN is quite curable.How is vulvar dysplasia (VIN) treated?
The mainstay of treatment is to remove all affected tissue with a margin of at least 2-3 mm of normal tissue around the VIN. For multiple lesions (multifocal), laser ablation is the most common treatment because it can destroy the abnormal cells without going too deep into normal tissue. For fewer or unifocal lesions, surgical excision is often performed to get a little deeper into the tissue and make sure there is not an early invasive cancer.
Is vulvar cancer easily curable or is it a "bad actor"?
Like many cancers, curability depends upon how early a cancer is found and treated. If a vulvar lesion shows less than a millimeter of invasion it is completely, 100% curable. If it invades more than 5 mm (about 1/4 inch), lymph nodes will already have cancer in them 40% of the time. Vulvar cancer spreads to the inguinal (groin) lymph nodes and when it does, it really changes the survival. Over 90% of women with vulvar cancer who have no lymph node involvement will live over 5 years. Survival at 5 years decreases to 75%, 36%, 24% and 0% in women with 1 or 2, 3 or 4, 5 or 6, or 7 or more lymph nodes positive for cancer removed at surgery. This poor survival is why doctors recommend biopsy of any suspicious lesion on the vulva to pick up a cancer early.