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Over the next 2 months we will dedicate this column to some general tips and pearls from the perspective of a gynecologic oncologist to guide general obstetrician gynecologists in the workup and management of preinvasive or invasive gynecologic diseases. The goal of these recommendations is to minimize misdiagnosis or delayed diagnosis and avoid unnecessary or untimely referrals.

Dr. Emma C. Rossi

Perform biopsy, not Pap smears, on visible cervical and vaginal lesions

The purpose of the Pap smear is to screen asymptomatic patients for cervical dysplasia or microscopic invasive disease. Cytology is an unreliable diagnostic tool for visible, symptomatic lesions in large part because of sampling errors, and the lack of architectural information in cytologic versus histopathologic specimens. Invasive lesions can be mischaracterized as preinvasive on a Pap smear. This can result in delayed diagnosis and unnecessary diagnostic procedures. For example, if a visible, abnormal-appearing, cervical lesion is seen during a routine visit and a Pap smear is performed (rather than a biopsy of the mass), the patient may receive an incorrect preliminary diagnosis of “high-grade dysplasia, carcinoma in situ” as it can be difficult to distinguish invasive carcinoma from carcinoma in situ on cytology. If the patient and provider do not understand the limitations of Pap smears in diagnosing invasive cancers, they may be falsely reassured and possibly delay or abstain from follow-up for an excisional procedure. If she does return for the loop electrosurgical excision procedure (LEEP), there might still be unnecessary delays in making referrals and definitive treatment while waiting for results. Radical hysterectomy may not promptly follow because, if performed within 6 weeks of an excisional procedure, it is associated with a significantly higher risk for perioperative complication, and therefore, if the excisional procedure was unnecessary to begin with, there may be additional time lost that need not be.1

Some clinicians avoid biopsy of visible lesions because they are concerned about bleeding complications that might arise in the office. Straightforward strategies to control bleeding are readily available in most gynecology offices, especially those already equipped for procedures such as LEEP and colposcopy. Prior to performing the biopsy, clinicians should ensure that they have supplies such as gauze sponges and ring forceps or packing forceps, silver nitrate, and ferric subsulfate solution (“Monsel’s solution”) close at hand. In the vast majority of cases, direct pressure for 5 minutes with gauze sponges and ferric subsulfate is highly effective at resolving most bleeding from a cervical or vaginal biopsy site. If this does not bring hemostasis, cautery devices or suture can be employed. If all else fails, be prepared to place vaginal packing (always with the insertion of a urinary Foley catheter to prevent urinary retention). In my experience, this is rarely needed.

Wherever possible, visible cervical or vaginal (or vulvar, see below) lesions should be biopsied for histopathology, sampling representative areas of the most concerning portion, in order to minimize misdiagnosis and expedite referral and definitive treatment. For necrotic-appearing lesions I recommend taking multiple samples of the tumor, as necrotic, nonviable tissue can prevent accurate diagnosis of a cancer. In general, Pap smears should be reserved as screening tests for asymptomatic women without visible pathology.
 

 

 

Don’t treat or refer low-grade dysplasia, even if persistent

Increasingly we are understanding that low-grade dysplasia of the lower genital tract (CIN I, VAIN I, VIN I) is less a precursor for cancer, and more a phenomenon of benign HPV-associated changes.2 This HPV change may be chronically persistent, may require years of observation and serial Pap smears, and may be a general nuisance for the patient. However, current guidelines do not recommend intervention for low-grade dysplasia of the lower genital tract.2 Interventions to resect these lesions can result in morbidity, including perineal pain, vaginal scarring, and cervical stenosis or insufficiency. Given the extremely low risk for progression to cancer, these morbidities do not outweigh any small potential benefit.

When I am conferring with patients who have chronic low-grade dysplasia I spend a great deal of time exploring their understanding of the diagnosis and its pathophysiology, their fears, and their expectation regarding “success” of treatment. I spend the time educating them that this is a sequela of chronic viral infection that will not be eradicated with local surgical excisions, that their cancer risk and need for surveillance would persist even if surgical intervention were offered, and that the side effects of treatment would outweigh any benefit from the small risk of cancer or high-grade dysplasia.

In summary, the treatment of choice for persistent low-grade dysplasia of the lower genital tract is comprehensive patient education, not surgical resection or referral to gynecologic oncology.
 

Repeat sampling if there’s a discordance between imaging and biopsy results

Delay in cancer diagnosis is one of the greatest concerns for front-line gynecology providers. One of the more modifiable strategies to avoid missed or delayed diagnosis is to ensure that there is concordance between clinical findings and testing results. Otherwise said: The results and findings should make sense in aggregate. An example was cited above in which a visible cervical mass demonstrated CIN III on cytologic testing. Another common example is a biopsy result of “scant benign endometrium” in a patient with postmenopausal bleeding and thickened endometrial stripe on ultrasound. In both of these cases there is clear discordance between physical findings and the results of pathology sampling. A pathology report, in all of its black and white certitude, seems like the most reliable source of information. However, always trust your clinical judgment. If the clinical picture is suggesting something far worse than these limited, often random or blind samplings, I recommend repeated or more extensive sampling (for example, dilation and curettage). At the very least, schedule close follow-up with repeated sampling if the symptom or finding persists. The emphasis here is on scheduled follow-up, rather than “p.r.n.,” because a patient who was given a “normal” pathology result to explain her abnormal symptoms may not volunteer that those symptoms are persistent as she may feel that anything sinister was already ruled out. Make certain that you explain the potential for misdiagnosis as the reason for why you would like to see her back shortly to ensure the issue has resolved.

 

Biopsy vulvar lesions, minimize empiric treatment

Vulvar cancer is notoriously associated with delayed diagnosis. Unfortunately, it is commonplace for gynecologic oncologists to see women who have vulvar cancers that have been empirically treated, sometimes for months or years, with steroids or other topical agents. If a lesion on the vulva is characteristically benign in appearance (such as condyloma or lichen sclerosis), it may be reasonable to start empiric treatment. However, all patients who are treated without biopsy should be rescheduled for a planned follow-up appointment in 2-3 months. If the lesion/area remains unchanged, or worse, the lesion should be biopsied before proceeding with a change in therapy or continued therapy. Once again, don’t rely on patients to return for evaluation if the lesion doesn’t improve. Many patients assume that our first empiric diagnosis is “gospel,” and therefore may not return if the treatment doesn’t work. Meanwhile, providers may assume that patients will know that there is uncertainty in our interpretation and that they will know to report if the initial treatment didn’t work. These assumptions are the recipe for delayed diagnosis. If there is too great a burden on the patient to schedule a return visit because of social or financial reasons then the patient should have a biopsy prior to initiation of treatment. As a rule, empiric treatment is not a good strategy for patients without good access to follow-up.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at [email protected].

References

1. Sullivan S. et al Gynecol Oncol. 2017 Feb;144(2):294-8.

2. Perkins R .et al J Low Genit Tract Dis. 2020 Apr;24(2):102-31.

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Over the next 2 months we will dedicate this column to some general tips and pearls from the perspective of a gynecologic oncologist to guide general obstetrician gynecologists in the workup and management of preinvasive or invasive gynecologic diseases. The goal of these recommendations is to minimize misdiagnosis or delayed diagnosis and avoid unnecessary or untimely referrals.

Dr. Emma C. Rossi

Perform biopsy, not Pap smears, on visible cervical and vaginal lesions

The purpose of the Pap smear is to screen asymptomatic patients for cervical dysplasia or microscopic invasive disease. Cytology is an unreliable diagnostic tool for visible, symptomatic lesions in large part because of sampling errors, and the lack of architectural information in cytologic versus histopathologic specimens. Invasive lesions can be mischaracterized as preinvasive on a Pap smear. This can result in delayed diagnosis and unnecessary diagnostic procedures. For example, if a visible, abnormal-appearing, cervical lesion is seen during a routine visit and a Pap smear is performed (rather than a biopsy of the mass), the patient may receive an incorrect preliminary diagnosis of “high-grade dysplasia, carcinoma in situ” as it can be difficult to distinguish invasive carcinoma from carcinoma in situ on cytology. If the patient and provider do not understand the limitations of Pap smears in diagnosing invasive cancers, they may be falsely reassured and possibly delay or abstain from follow-up for an excisional procedure. If she does return for the loop electrosurgical excision procedure (LEEP), there might still be unnecessary delays in making referrals and definitive treatment while waiting for results. Radical hysterectomy may not promptly follow because, if performed within 6 weeks of an excisional procedure, it is associated with a significantly higher risk for perioperative complication, and therefore, if the excisional procedure was unnecessary to begin with, there may be additional time lost that need not be.1

Some clinicians avoid biopsy of visible lesions because they are concerned about bleeding complications that might arise in the office. Straightforward strategies to control bleeding are readily available in most gynecology offices, especially those already equipped for procedures such as LEEP and colposcopy. Prior to performing the biopsy, clinicians should ensure that they have supplies such as gauze sponges and ring forceps or packing forceps, silver nitrate, and ferric subsulfate solution (“Monsel’s solution”) close at hand. In the vast majority of cases, direct pressure for 5 minutes with gauze sponges and ferric subsulfate is highly effective at resolving most bleeding from a cervical or vaginal biopsy site. If this does not bring hemostasis, cautery devices or suture can be employed. If all else fails, be prepared to place vaginal packing (always with the insertion of a urinary Foley catheter to prevent urinary retention). In my experience, this is rarely needed.

Wherever possible, visible cervical or vaginal (or vulvar, see below) lesions should be biopsied for histopathology, sampling representative areas of the most concerning portion, in order to minimize misdiagnosis and expedite referral and definitive treatment. For necrotic-appearing lesions I recommend taking multiple samples of the tumor, as necrotic, nonviable tissue can prevent accurate diagnosis of a cancer. In general, Pap smears should be reserved as screening tests for asymptomatic women without visible pathology.
 

 

 

Don’t treat or refer low-grade dysplasia, even if persistent

Increasingly we are understanding that low-grade dysplasia of the lower genital tract (CIN I, VAIN I, VIN I) is less a precursor for cancer, and more a phenomenon of benign HPV-associated changes.2 This HPV change may be chronically persistent, may require years of observation and serial Pap smears, and may be a general nuisance for the patient. However, current guidelines do not recommend intervention for low-grade dysplasia of the lower genital tract.2 Interventions to resect these lesions can result in morbidity, including perineal pain, vaginal scarring, and cervical stenosis or insufficiency. Given the extremely low risk for progression to cancer, these morbidities do not outweigh any small potential benefit.

When I am conferring with patients who have chronic low-grade dysplasia I spend a great deal of time exploring their understanding of the diagnosis and its pathophysiology, their fears, and their expectation regarding “success” of treatment. I spend the time educating them that this is a sequela of chronic viral infection that will not be eradicated with local surgical excisions, that their cancer risk and need for surveillance would persist even if surgical intervention were offered, and that the side effects of treatment would outweigh any benefit from the small risk of cancer or high-grade dysplasia.

In summary, the treatment of choice for persistent low-grade dysplasia of the lower genital tract is comprehensive patient education, not surgical resection or referral to gynecologic oncology.
 

Repeat sampling if there’s a discordance between imaging and biopsy results

Delay in cancer diagnosis is one of the greatest concerns for front-line gynecology providers. One of the more modifiable strategies to avoid missed or delayed diagnosis is to ensure that there is concordance between clinical findings and testing results. Otherwise said: The results and findings should make sense in aggregate. An example was cited above in which a visible cervical mass demonstrated CIN III on cytologic testing. Another common example is a biopsy result of “scant benign endometrium” in a patient with postmenopausal bleeding and thickened endometrial stripe on ultrasound. In both of these cases there is clear discordance between physical findings and the results of pathology sampling. A pathology report, in all of its black and white certitude, seems like the most reliable source of information. However, always trust your clinical judgment. If the clinical picture is suggesting something far worse than these limited, often random or blind samplings, I recommend repeated or more extensive sampling (for example, dilation and curettage). At the very least, schedule close follow-up with repeated sampling if the symptom or finding persists. The emphasis here is on scheduled follow-up, rather than “p.r.n.,” because a patient who was given a “normal” pathology result to explain her abnormal symptoms may not volunteer that those symptoms are persistent as she may feel that anything sinister was already ruled out. Make certain that you explain the potential for misdiagnosis as the reason for why you would like to see her back shortly to ensure the issue has resolved.

 

Biopsy vulvar lesions, minimize empiric treatment

Vulvar cancer is notoriously associated with delayed diagnosis. Unfortunately, it is commonplace for gynecologic oncologists to see women who have vulvar cancers that have been empirically treated, sometimes for months or years, with steroids or other topical agents. If a lesion on the vulva is characteristically benign in appearance (such as condyloma or lichen sclerosis), it may be reasonable to start empiric treatment. However, all patients who are treated without biopsy should be rescheduled for a planned follow-up appointment in 2-3 months. If the lesion/area remains unchanged, or worse, the lesion should be biopsied before proceeding with a change in therapy or continued therapy. Once again, don’t rely on patients to return for evaluation if the lesion doesn’t improve. Many patients assume that our first empiric diagnosis is “gospel,” and therefore may not return if the treatment doesn’t work. Meanwhile, providers may assume that patients will know that there is uncertainty in our interpretation and that they will know to report if the initial treatment didn’t work. These assumptions are the recipe for delayed diagnosis. If there is too great a burden on the patient to schedule a return visit because of social or financial reasons then the patient should have a biopsy prior to initiation of treatment. As a rule, empiric treatment is not a good strategy for patients without good access to follow-up.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at [email protected].

References

1. Sullivan S. et al Gynecol Oncol. 2017 Feb;144(2):294-8.

2. Perkins R .et al J Low Genit Tract Dis. 2020 Apr;24(2):102-31.

Over the next 2 months we will dedicate this column to some general tips and pearls from the perspective of a gynecologic oncologist to guide general obstetrician gynecologists in the workup and management of preinvasive or invasive gynecologic diseases. The goal of these recommendations is to minimize misdiagnosis or delayed diagnosis and avoid unnecessary or untimely referrals.

Dr. Emma C. Rossi

Perform biopsy, not Pap smears, on visible cervical and vaginal lesions

The purpose of the Pap smear is to screen asymptomatic patients for cervical dysplasia or microscopic invasive disease. Cytology is an unreliable diagnostic tool for visible, symptomatic lesions in large part because of sampling errors, and the lack of architectural information in cytologic versus histopathologic specimens. Invasive lesions can be mischaracterized as preinvasive on a Pap smear. This can result in delayed diagnosis and unnecessary diagnostic procedures. For example, if a visible, abnormal-appearing, cervical lesion is seen during a routine visit and a Pap smear is performed (rather than a biopsy of the mass), the patient may receive an incorrect preliminary diagnosis of “high-grade dysplasia, carcinoma in situ” as it can be difficult to distinguish invasive carcinoma from carcinoma in situ on cytology. If the patient and provider do not understand the limitations of Pap smears in diagnosing invasive cancers, they may be falsely reassured and possibly delay or abstain from follow-up for an excisional procedure. If she does return for the loop electrosurgical excision procedure (LEEP), there might still be unnecessary delays in making referrals and definitive treatment while waiting for results. Radical hysterectomy may not promptly follow because, if performed within 6 weeks of an excisional procedure, it is associated with a significantly higher risk for perioperative complication, and therefore, if the excisional procedure was unnecessary to begin with, there may be additional time lost that need not be.1

Some clinicians avoid biopsy of visible lesions because they are concerned about bleeding complications that might arise in the office. Straightforward strategies to control bleeding are readily available in most gynecology offices, especially those already equipped for procedures such as LEEP and colposcopy. Prior to performing the biopsy, clinicians should ensure that they have supplies such as gauze sponges and ring forceps or packing forceps, silver nitrate, and ferric subsulfate solution (“Monsel’s solution”) close at hand. In the vast majority of cases, direct pressure for 5 minutes with gauze sponges and ferric subsulfate is highly effective at resolving most bleeding from a cervical or vaginal biopsy site. If this does not bring hemostasis, cautery devices or suture can be employed. If all else fails, be prepared to place vaginal packing (always with the insertion of a urinary Foley catheter to prevent urinary retention). In my experience, this is rarely needed.

Wherever possible, visible cervical or vaginal (or vulvar, see below) lesions should be biopsied for histopathology, sampling representative areas of the most concerning portion, in order to minimize misdiagnosis and expedite referral and definitive treatment. For necrotic-appearing lesions I recommend taking multiple samples of the tumor, as necrotic, nonviable tissue can prevent accurate diagnosis of a cancer. In general, Pap smears should be reserved as screening tests for asymptomatic women without visible pathology.
 

 

 

Don’t treat or refer low-grade dysplasia, even if persistent

Increasingly we are understanding that low-grade dysplasia of the lower genital tract (CIN I, VAIN I, VIN I) is less a precursor for cancer, and more a phenomenon of benign HPV-associated changes.2 This HPV change may be chronically persistent, may require years of observation and serial Pap smears, and may be a general nuisance for the patient. However, current guidelines do not recommend intervention for low-grade dysplasia of the lower genital tract.2 Interventions to resect these lesions can result in morbidity, including perineal pain, vaginal scarring, and cervical stenosis or insufficiency. Given the extremely low risk for progression to cancer, these morbidities do not outweigh any small potential benefit.

When I am conferring with patients who have chronic low-grade dysplasia I spend a great deal of time exploring their understanding of the diagnosis and its pathophysiology, their fears, and their expectation regarding “success” of treatment. I spend the time educating them that this is a sequela of chronic viral infection that will not be eradicated with local surgical excisions, that their cancer risk and need for surveillance would persist even if surgical intervention were offered, and that the side effects of treatment would outweigh any benefit from the small risk of cancer or high-grade dysplasia.

In summary, the treatment of choice for persistent low-grade dysplasia of the lower genital tract is comprehensive patient education, not surgical resection or referral to gynecologic oncology.
 

Repeat sampling if there’s a discordance between imaging and biopsy results

Delay in cancer diagnosis is one of the greatest concerns for front-line gynecology providers. One of the more modifiable strategies to avoid missed or delayed diagnosis is to ensure that there is concordance between clinical findings and testing results. Otherwise said: The results and findings should make sense in aggregate. An example was cited above in which a visible cervical mass demonstrated CIN III on cytologic testing. Another common example is a biopsy result of “scant benign endometrium” in a patient with postmenopausal bleeding and thickened endometrial stripe on ultrasound. In both of these cases there is clear discordance between physical findings and the results of pathology sampling. A pathology report, in all of its black and white certitude, seems like the most reliable source of information. However, always trust your clinical judgment. If the clinical picture is suggesting something far worse than these limited, often random or blind samplings, I recommend repeated or more extensive sampling (for example, dilation and curettage). At the very least, schedule close follow-up with repeated sampling if the symptom or finding persists. The emphasis here is on scheduled follow-up, rather than “p.r.n.,” because a patient who was given a “normal” pathology result to explain her abnormal symptoms may not volunteer that those symptoms are persistent as she may feel that anything sinister was already ruled out. Make certain that you explain the potential for misdiagnosis as the reason for why you would like to see her back shortly to ensure the issue has resolved.

 

Biopsy vulvar lesions, minimize empiric treatment

Vulvar cancer is notoriously associated with delayed diagnosis. Unfortunately, it is commonplace for gynecologic oncologists to see women who have vulvar cancers that have been empirically treated, sometimes for months or years, with steroids or other topical agents. If a lesion on the vulva is characteristically benign in appearance (such as condyloma or lichen sclerosis), it may be reasonable to start empiric treatment. However, all patients who are treated without biopsy should be rescheduled for a planned follow-up appointment in 2-3 months. If the lesion/area remains unchanged, or worse, the lesion should be biopsied before proceeding with a change in therapy or continued therapy. Once again, don’t rely on patients to return for evaluation if the lesion doesn’t improve. Many patients assume that our first empiric diagnosis is “gospel,” and therefore may not return if the treatment doesn’t work. Meanwhile, providers may assume that patients will know that there is uncertainty in our interpretation and that they will know to report if the initial treatment didn’t work. These assumptions are the recipe for delayed diagnosis. If there is too great a burden on the patient to schedule a return visit because of social or financial reasons then the patient should have a biopsy prior to initiation of treatment. As a rule, empiric treatment is not a good strategy for patients without good access to follow-up.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no relevant financial disclosures. Email her at [email protected].

References

1. Sullivan S. et al Gynecol Oncol. 2017 Feb;144(2):294-8.

2. Perkins R .et al J Low Genit Tract Dis. 2020 Apr;24(2):102-31.

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