- Email: [email protected]
Imaging in vulval cancer
Best Practice & Research Clinical Obstetrics & Gynaecology Vol. 17, No. 4, pp. 543 –556, 2003 doi:10.1016/S1521-6934(03)00040-3, www.elsevier.com/locate/jnlabr/ybeog
2 Imaging in vulval cancer S. A. A. Sohaib*
BSc, MRCP, FRCR
Consultant Radiologist
E. C. Moskovic
FRCP, FRCR
Consultant Radiologist Department of Diagnostic Imaging, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
Cancer of the vulva spreads locally and, almost without exception, to the regional nodes in the groin to the superficial then deep inguinal groups and the pelvic nodes in a step-wise fashion. Because the single most important prognostic factor is the presence or absence of nodal disease, accurate diagnosis of nodal involvement is paramount. In the past, the status of inguinal nodes in vulval cancer has been ascertained only following groin node dissection, except in those cases with clinically obviously groin nodes. However, as up to 70% of patients at all stages of disease have negative nodes histologically, and as up to 70% of patients have groin or lower-limb problems after radical groin surgery, this approach incurs ‘unnecessary’ surgery for the majority of patients with the attendant morbidity. Using new diagnostic imaging methods, detection and assessment of groin lymph nodes has been developing over the past few years with the ultimate intention of reducing groin node surgery in node-negative patients. In this chapter we review the role of imaging in patients with vulval cancer in which there is a greater role in the assessment of nodal disease rather than in the assessment of the cancer on the vulva. Key words: vulval cancer; lymph node; ultrasound; magnetic resonance imaging.
Vulval cancer is an uncommon gynaecological malignancy, affecting mainly the elderly. Women with vulval carcinoma are assessed clinically with examination of the vulva and the groin, and this may involve an examination under anaesthesia. Full-thickness biopsy(s) of the lesion is important to confirm the diagnosis and to determine the extent of the lesion. The most important prognostic factors include size of the primary lesion and involvement of the regional lymph nodes. Both of these features are incorporated into the FIGO staging of the tumour (see Table 1).1,2 The standard treatment for several decades had been radical vulvectomy with bilateral inguinofemoral lymphadenectomy. This radical approach had significant morbidity.3 There has now been a trend to a more conservative surgical approach to both the vulval and the groin phase.3 The purpose of radical groin lymphadenectomy is for diagnostic and therapeutic benefit. Doubt remains about the therapeutic role, especially in node-negative patients. Diagnostic imaging techniques may be used in the detection * Corresponding author. Tel.: þ44-207-808-2343; Fax: 44-207-352-0726. E-mail address: [email protected] (S. A. A. Sohaib). 1521-6934/$ - see front matter Q 2003 Elsevier Ltd. All rights reserved.
544 S. A. A. Sohaib and E. C. Moskovic
Table 1. Staging of the carcinoma of the vulva.1,2 T1 T2 T3 T4 N0 N1 N2 M0 M1
Tumour less than 2 cm in the greatest dimension and confined to vulva or perineum Tumour more than 2 cm in the greatest dimension and confined to the vulva or perineum Tumour invading any of the following: lower urethra, vagina or anus Tumour invading any of the following: upper urethra, bladder mucosa, rectal mucosa, and pelvic bone No regional lymph node metastasis Unilateral lymph node metastasis Bilateral lymph node metastasis No distant metastasis Distant metastasis (including pelvic lymph nodes metastasis)
FIGO Stage Grouping T1, N0, M0 T2, N0, M0 T1 or T2, N1, M0 T3, N0 or N1, M0 IVA T1 or T2 or T3, N2, M0 T4, any N, M0 IVB Any T, any N, M1 I II III
and assessment of groin lymph nodes for metastatic disease with the intention of reducing groin-node surgery.
PRIMARY VULVAL CANCER Cancer of the vulva involves the labia in about two-thirds of patients, with other sites involved in the remaining third.3 Vulval cancer usually spreads slowly and infiltrates local tissues before involving the lymph nodes in the groin. Local spread can extend to involve the vagina, urethra and anus and rarely to the urethra, bladder and bone. In more advanced cases the pelvic nodes can be affected. Disease outside the pelvis is rare in vulval cancer with the exception of malignant melanoma and rare sarcomas. Imaging techniques have had a relatively limited role in the assessment of the primary tumour as this is readily assessed clinically, especially as small lesions are often not identified with imaging. However, magnetic resonance imaging (MRI) has been shown to identify primary vulval cancer accurately4 (Figures 1 and 2). When the tumour is seen on MRI the extent of tumour can also be outlined. Most tumours show a typical signal intensity pattern of low signal intensity on T1-weighted images and moderate to high signal intensity on T2-weighted images. We have also found that intravenous gadolinium was not helpful in the identification of the primary lesion, and small primary tumours and tumours that were not thick (i.e. plaque-like lesions) were not seen.4 This may have been due to the fact that the imaging parameters were not optimal for the identification of small primary lesions in this retrospective study. Using high-resolution imaging with a small field of view and thinner sections may have identified more primary lesions. MR imaging is likely to be of more benefit in the assessment of more locally advanced disease as the multi-planar imaging capability may be helpful in assessing involvement of other pelvic organs. Using optimal MR imaging techniques, deep extension of the primary
Imaging in Vulval cancer 545
Figure 1. MRI of carcinoma of vulva. Axial T2-weighted fast spin-echo MR image shows 3-cm tumour (arrow) arising from right labia.
Figure 2. MRI of a large central carcinoma of vulva (straight arrow) involving clitoris (curved arrow). Axial T2-weighted fast spin-echo MR image shows intermediate-signal-intensity tumour extending up to involve clitoris.
546 S. A. A. Sohaib and E. C. Moskovic
tumour and assessment of adjacent pelvic structures (e.g. anal sphincter) may be better assessed by MR imaging than clinical examination but this requires further study.
LYMPH NODE SPREAD Lymphatic drainage of the vulva is to the inguinal and femoral nodes in the groin. The superficial inguinal nodes are just below the skin along the medial two-thirds of the inguinal ligament and along the saphenous vein close to the sapheno –femoral junction. The inguinal nodes are the primary nodes which drain the vulva, and these, in turn, drain into the deep femoral nodes located along the femoral artery and vein. From there the lymphatic drainage is to the external iliac lymph nodes, the lowest of which is at the entrance of the femoral canal; it is known as the Cloquet node and is an important indicator of the likelihood of metastatic spread to the pelvic nodes. Drainage from the midline structures, such as the perineum and clitoris, is to both groins, and there is some contralateral drainage from other parts of the vulva (large Bartholin cancer). A truly lateral vulval cancer spreads to the ipsilateral regional nodes.5 Pelvic node involvement is uncommon and is secondary to groin node involvement. For central vulval cancers there is very rarely direct spread to the pelvic nodes via the internal pudendal vessels. Complete obstruction of the lymphatics can lead to involvement of the subcutaneous and dermal lymphatics of the vulva, upper thigh and lower abdomen. The status of the groin node spread is the important prognostic marker. Patients with negative groin nodes have an approximately 90% survival whereas patients with positive nodes have a survival of approximately 50%.6 In the past, the status of clinically non-suspicious inguinal nodes in vulval cancer has been ascertained only following groin node dissection. However, as up to 70% of patients at all stages of disease have negative nodes, this approach incurs unnecessary surgery with the attendant morbidity for the majority of patients.3 Clinical palpation is usually restricted to the superficial nodes, and, as a method for detecting groin lymph node metastases, it is unreliable, with a sensitivity of 57% and a specificity of 62%.7 Modern diagnostic imaging, however, is increasingly capable of detecting whether a lymph node contains metastatic disease with a sensitivity and specificity that make them potentially very useful clinically.
RECURRENT DISEASE Most recurrent vulval cancers arise in the vulva, or groins. In some patients the recurrence is in the skin bridge—the tissue between the vulval and groin incisions; in other patients there may be pelvic nodal metastases. Disease outside the pelvis is rare except for the less common vulval cancers, including malignant melanoma. Commonly the recurrence is easily assessed clinically, although in some patients a formal examination under anaesthesia may be necessary. Exclusion of pelvic or more distant disease (including chest metastases) is important before radical treatment is undertaken. For deep-seated recurrences, for example from Bartholin gland carcinoma, or angiosarcoma, either Computed tomography (CT) or MRI can be useful in assessing the extent of disease, and whether, for example, there is bone involvement. Extension of disease to the anal canal, urethra or bladder is best determined by thorough clinical assessment and biopsies.
Imaging in Vulval cancer 547
ASSESSMENT OF RADIOLOGICAL IMAGING TECHNIQUES Ultrasound (USS) The advent of high-resolution, high-frequency (7– 15 MHz) ultrasound has proved extremely useful in the evaluation of regional lymph nodes for metastatic disease, although not all authors agree.8 – 10 This technique allows detection of nodes as small as 5 mm within the superficial soft tissues and facilitates fine-needle aspiration for cytology (FNAC). Ultrasound evaluation of lymph nodes is now used routinely in staging head and neck tumours, melanoma and some breast cancers and has recently been applied, with fine-needle aspiration cytology (FNAC), to compliment staging of vulval cancer with a high level of sensitivity and specificity.11,12 On ultrasound, normal nodes (Figure 3) are oval in shape and have an echogenic hilus with a hypoechoic lymphoid cortex. A fatty node may be isoechoic with the surrounding fatty stroma. Normal lymph nodes are typically under 1 cm in diameter but this can be variable, with benign reactive nodes as large, i.e. 2 – 3 cm. Lymph nodes with metastatic disease (Figure 4) tend to develop a rounded shape, and a ratio of long/short axis diameter of the node of less than 2 is taken to indicate malignancy.13,14 Other useful sonographic features are loss of the echogenic hilar sinus fat, irregular margin and increasing low attenuation of the cortex.11 Doppler evaluation on ultrasound can further aid in the characterization of lymph nodes. Colour and power Doppler pattern in metastatic nodes demonstrate more peripheral vascularity than reactive nodes, which have more hilar perfusion. This relates
Figure 3. Ultrasound of normal node with oval contour, peripheral low attenuation lymphoid tissue and higher attenuation central medullary sinus tissue.
548 S. A. A. Sohaib and E. C. Moskovic
Figure 4. Ultrasound of metastatic lymph node. The node is large and rounded with internal heterogeneity.
to the abnormal distribution of vessels within malignant nodes, with peripheral foci of tumour causing neovascularity locally within the marginal and medullary sinuses.15 Spectral waveform analysis may also be used to distinguish benign from malignant nodes, nodes with high resistive index being almost always involved by tumour.16 Ultrasound assessment of lymph nodes can be combined with FNAC. Ultrasound can be used to guide the cytological assessment of suspicious nodes (Figure 5). The technique is carried out under local anaesthetic, and aspiration using a 21G needle is performed with real-time ultrasound guidance. In the original report on these techniques using morphological criteria, a sensitivity of 85% and a specificity of 83% were reported.11 Cytology of groin nodes had a specificity 100% but a sensitivity of only 58% owing to a high false-negative rate from sampling error.11 Recently, data suggest that the combination of ultrasound-guided FNAC of nodes considered suspicious on ultrasound criteria has a sensitivity and specificity approaching 100% for the detection of metastatic disease12 (see Table 2). There are, however, a number of limitations with ultrasound and cytology. First, there is a learning curve for the technique—but this can be overcome with training and experience. Second, there is a diagnostic overlap in the appearance of benign reactive and metastatic nodes. Third, a lymph node may appear abnormal and contain metastatic disease but the aspirate fails to obtain abnormal cells. This relates to sampling error and can be difficult to overcome in a small node where placement of the needle is exacting. Lastly, small-volume micrometastases within lymph nodes deemed normal on ultrasound criteria remain a diagnostic challenge because they are beyond the resolution of current technology. However, routine histological sampling of lymph
Imaging in Vulval cancer 549
Figure 5. Aspiration needle (arrow) in situ in a metastatic lymph node during fine-needle aspiration for cytology (FNAC) procedures.
nodes will also not detect micro-metastasis, except by chance in a random section, as only a small volume of the lymph node is actually examined microscopically. In patients who are being monitored serially using ultrasound, a follow-up scan at 2 –3 months will detect nodes as they enlarge and become sonographically abnormal. It is already our practice in patients who have been unsuitable for, or reluctant to have, groin node surgery following the diagnosis of early-stage vulval carcinoma, to undertake initial groin node ultrasound with FNAC. If the groin nodes are sonographically and cytologically benign, then 3-monthly ultrasound is undertaken, with FNAC only if the nodes become suspicious on ultrasound criteria. Indeed, in malignant melanoma, USS has been used as a means of nodal surveillance.17 We plan to embark on a randomized controlled trial on the use of groin USS/FNAC in the management of the groin nodes in primary squamous-cell cancer of the vulva. Table 2. Lymph node assessment.
Ultrasound Cytology Combined
Sensitivity (95% CI)
Specificity (95% CI)
86 (67–96) 75 (55–89) 93 (76–99)
96 (85–99) 100 (92–100) 100 (92–100)
Reproduced from Hall TB, et al (2003, Clinical Radiology, in press) with permission.
550 S. A. A. Sohaib and E. C. Moskovic
CT scanning in vulval cancer Computed tomography (CT) has been used in the radiological imaging of all gynaecological cancers; it has the least impact on the clinical management of vulval cancer. There were some early reports about its usefulness in assessing pelvic anatomy.18 Its role has been superseded to some extent by MRI—in which there is the facility to reconstruct sagittal and coronal images. It may still have a place in the assessment of rare vulval cancers such as the angiosarcoma, but it is inferior to clinical examination. In a recent review of the use of CT scanning in our institution, we found that it did not contribute to clinical management and, as a result, we no longer routinely use CT scanning in patients with vulval cancer.19
Magnetic resonance imaging (MRI) MRI has a number of advantages for evaluating lymph nodes. Vessels and lymph nodes can be differentiated without the use of intravenous contrast media, and its superior contrast resolution permits the detection of small nodes. On MR the cross-sectional images also allow assessment of the depth of the nodes from the skin surface, which can vary markedly depending of the patient’s body habitus.20,21 This information could be invaluable in the planning of external beam radiotherapy. Furthermore, MR images allow for precise anatomical localization of abnormal lymph nodes—which may help in surgical planning. On MRI it is possible to identify three inguinal node groups.21 The proximal superficial group of nodes lies superficial to the inguinal ligament and above the level of the sapheno – femoral junction. The distal superficial group lies superficial to the inguinal ligament and at or below the level of the sapheno – femoral junction. The deep ingiuinal nodes are sited deeply medial to the common femoral vein at or cranial to the sapheno – femoral junction.21 Groin lymph nodes can be detected easily on MRI (Figure 6). In cross-sectional imaging techniques, size has been the main criterion for distinguishing between benign and malignant lymph nodes. There is agreement that measurement of the maximum short axis diameter is a more reliable criterion than the maximum long axis diameter.22, 23 The number and size of lymph nodes on MRI varies considerably.21 The sensitivity and specificity of detecting abnormal lymph nodes depends on the threshold used to categorize normal from abnormal nodes. Using a size criterion of abnormality of 10 mm or greater in short-axis diameter for superficial inguinal nodes, the reported sensitivity for detection of malignant nodes was 40% and the specificity 97%.4 For deep inguinal nodes, if nodes 8 mm or greater in short-axis diameter are considered abnormal then the sensitivity for detection of malignant nodes was 50% and the specificity 100%.4 The use of these size criteria of abnormal lymph nodes gives a high specificity but low sensitivity. A test with high specificity would have few false negatives and therefore if a node were enlarged the surgeon would have a high degree of confidence that the lymph node was involved. Therefore, if the patient was a poor-risk candidate for surgery then arguably non-surgical therapy could be used. Other investigators have tried to use other criteria on imaging to distinguish benign from malignant nodes. We did not find the number of lymph nodes in the groin useful in determining affected from unaffected groins. Signal intensity or T1 and T2 relaxation times has not been found to be useful in distinguishing between benign and malignant nodes.24
Imaging in Vulval cancer 551
Figure 6. Two metastatic lymph nodes in the left groin seen on (A) axial T2-weighted fast spin-echo MR image and on (B) left groin ultrasound.
552 S. A. A. Sohaib and E. C. Moskovic
In another MR study using high-resolution imaging with surface coil; the criteria considered suspicious for malignancy were (i) long-axis diameter greater than 21 mm, (ii) short-axis diameter greater than 10 mm, (iii) long-to-short axis ratio less than 1.3:1, and (iv) irregularity of contour and cystic change within solid parts of a lymph node.25 The most useful observations on MRI for identifying metastatic lymph nodes were contour irregularity and cystic change. MR imaging can be compared with other cross-sectional imaging techniques, i.e. ultrasound and computed tomography (CT). CTevaluation of lymph nodes is similar to that with MRI, with size criteria used to identify abnormal nodes. Ultrasound is cheaper and more readily available than MRI and it can be easily used to guide FNAC. The need for a relatively long examination by a skilled radiologist or sonographer is a disadvantage over the MRI technique. An unsupervized radiographer can routinely run the MR protocol, the images subsequently being read by any radiologist familiar with the criteria used. MR images are also more reproducible for comparison with baseline studies when looking for change in lymph node size or morphology that might indicate the development of metastases. It would remain possible to use ultrasound-guided biopsy to sample any equivocal lymph node given that the relationship of the lymph node to the vessels is clearly depicted on MRI. Finally, not all patients can undergo an MRI scan because of fear, and cardiac pacemakers, for example. MR lymphography More recently ultra-small-iron-oxide-particle (USIOP) has become available for MR lymphography.26 – 28 These are iron oxide nano-particles (20 nm) coated with lowmolecular-weight dextran. The generic name for this agent is feruxtram; it is marketed in Europe under the name of Sinerem and in the USA as Comibdex. USIOP is administered intravenously. The iron oxide particles are taken up by the macrophages of the lymph nodes, where they accumulate. They reduce the signal intensity of normally functioning nodes on post-contrast T2- and T2p-weighted images through the magnetic susceptibility effects of iron oxide. Lymph nodes with metastatic disease, in which macrophages are replaced by tumour cells, do not accumulate the iron oxide and therefore show no significant change in signal intensity on post-contrast T2- and T2pweighted images. Early clinical experience suggests that USIOP-enhanced MR lymphography improves the sensitivity and specificity for the detection of nodal metastases and suggests that micro-metastases could be detected in normal-sized nodes.27 Larger studies in a number of centres in Europe and the USA are currently ongoing. Our early experience with MR lymphography in pelvic malignancy has shown that, compared to the conventional MR imaging criterion, i.e. lymph node size, MR lymphography is more sensitive at detecting involved lymph nodes.29 The sensitivity was improved from 55 to 89% while specificity was 89%.29 Positron emission tomography (PET) PET with 18F-FDG has been used as a functional method of determining tumour viability in several cancers.30 This method is based on the increased cellular glucose uptake that is associated with malignancy. PET has also been investigated in the evaluation of groin nodes in vulval cancer.31,32 A study in 15 patients, using the tracer 18-fluorodeoxyglucose, showed that PET imaging was relatively insensitive in predicting lymph node metastasis, it had a sensitivity of 67%, a specificity of 95%, a positive predictive value of 86% and a negative predictive value of 86%.32 PETwas more accurate
Imaging in Vulval cancer 553
in detecting extranodal metastases than disease confined within the groin nodes.32 A further PET study in 25 patients, with L-[1-11C]-tyrosine (TYR) as tracer, showed that, in the detection of inguino-femoral lymph node metastases, PET was not superior to palpation.31 The sensitivity, specificity, accuracy and positive and negative predictive values for TYR-PET were, respectively, 53, 95, 94, 33 and 98% per lymph node and 75, 62, 65, 41 and 88 per groin.31 The technique is still being evaluated and may not be a practical affordable option. Lymphoscintigraphy—imaging for sentinel lymph node biopsy The concept of excision and histological assessment of the sentinel node in vulval cancer—to decrease the morbidity associated with groin dissection—has become a topic of interest in gynaecological oncology.33 – 37 The sentinel node is defined as the first node in the lymphatic chain or basin that receives primary lymphatic flow from the suspected lesion. This node is used as a representative of the entire lymph node basin and, in theory, is the first site of metastatic disease in a lymph node. If the sentinel node is negative for metastatic disease the remainder of the nodes should also be free of tumour, thereby avoiding unnecessary surgery. Lymphoscintigraphy in vulval cancer—which was first described in a pilot study to test the feasibility of the technique—was not used to detect metastatic disease in lymph nodes or to identify the sentinel node.33 Various techniques have been described. The radioactive tracer commonly used is technetium 99 m (Tc-99 m) which is usually linked to sulphur colloid or to human albumin; however, other tracers—such phytate—have been used.37 The radioactive tracer is injected intra-lesionally or peri-lesionally. Imaging can be performed pre-operatively and/or intra-operatively using hand-held gamma probes to identify the nodes that have taken up the radioactive tracer. Lymphoscintigraphy may also be combined with the blue-dye technique for identifying sentinel nodes.36 The major advantage of using the sentinel node approach in early vulval cancer is to decrease the associated morbidity of groin dissection. However, there are major drawbacks. First, there is no evidence to suggest that superficial inguinal node dissection alone results in a decreased incidence of lymphoedema as compared with complete lymphadenectomy. Second, metastasis to the deep inguinal or femoral nodes has been found without evidence of superficial node disease.38 A GOG study revealed a high incidence of groin recurrence after performing only superficial groin dissection, and this modification of groin node dissection is no longer recommended.39 Other drawbacks to sentinel node biopsy include the need for operator experience; moreover, logistically, performing the procedures can be demanding, with the need for co-ordination of the patient between different departments.
SUMMARY Imaging has a limited role in the evaluation of primary site of disease in vulval cancer as this is readily assessed clinically. For larger cancers MR imaging may be helpful in evaluating the extent of disease in patients with advanced tumour involving the perineum, vagina and anal canal. Groin lymphadenectomy is performed for diagnostic and therapeutic reasons, and groin node status is the most important prognostic factor. Clinical palpation is unreliable, but a number of diagnostic imaging techniques may be of value in detecting metastases with the aim of permitting a more conservative approach
554 S. A. A. Sohaib and E. C. Moskovic
to the management of groin nodes. Ultrasound combined with FNAC offers a quick and easy method and is a highly specific method for identifying involved lymph nodes. New MR imaging techniques and MR lymphography requires further evaluation. Sentinel node biopsy offers another exciting possibility.
ACKNOWLEDGEMENTS We would like to thank Mrs Janet MacDonald for assistance with the illustrations.
Practice points † primary tumour is best assessed clinically. For advanced tumours, deep extension of the primary tumour, and assessment of adjacent pelvic structures (e.g. anal sphincter) clinical assessment may be supplemented with MR imaging † the disease status of the regional groin lymph nodes is the most important prognostic factor in vulval cancer. Hence, this influences the decision to perform radical of conservative treatment † combined ultrasound and FNAC provide sensitive and specific tools for preoperative assessment and may prevent unnecessary groin dissection and attendant morbidity in selected patients with vulval cancer
Research agenda † outcome of patients selected for conservative treatment following combined ultrasound and FNAC † use of MR lymphography in vulval cancer † validation of sentinel lymph node biopsy in vulval cancer in a large multi-centre trail † outcome of patients selected for conservative or radical surgery following sentinel lymph node biospy
REFERENCES 1. International Union Against Cancer [UICC]: TNM classification of malignant tumours, 5th edn. New York: Wiley-Liss, 1997. 2. Benedet JL, Bender H, Jones Jr. H et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. International Journal of Gynaecology and Obstetrics 2000; 70: 209 –262. * 3. Cavanagh D & Hoffman MS. Controversies in the management of vulvar carcinoma. British Journal of Obstetrics and Gynaecology 1996; 103: 293–300. * 4. Sohaib SA, Richards PS, Ind Tet al. MR imaging of carcinoma of the vulva. American Journal of Roentgenology 2002; 178: 373–377. 5. Iversen T & Aas M. Lymphatics of the vulva. British Journal of Obstetrics & Gynaecology 1963; 70: 751–765. 6. Ghurani GB & Penalver MA. An update on vulvar cancer. American Journal of Obstetrics and Gynecology 2001; 185: 294 –299. 7. Piura B, Rabinovich A, Cohen Yet al. Squamous cell carcinoma of the vulva in the south of Israel: a study of 50 cases. Journal of Surgical Oncology 1998; 67: 174–181.
Imaging in Vulval cancer 555 8. Makela PJ, Leminen A, Kaariainen M & Lehtovirta P. Pretreatment sonographic evaluation of inguinal lymh nodes in patients with vulval malignancy. Journal of Ultrasound Medicine 1993; 5: 255–258. 9. Dragoni F, Cartoni C, Pescarmona E et al. The role of high resolution pulsed and color Doppler ultrasound in the differential diagnosis of benign and malignant lymphadenectomy. Cancer 1999; 85: 2485– 2490. 10. Abang Mohammed DK, Uberoi R, de B Lopes A & Monaghan JM. Inguinal node status by ultrasound in vulvar cancer. Gynecologic Oncology 2000; 77: 825–830. * 11. Moskovic EC, Shepherd JH, Barton DP et al. The role of high resolution ultrasound with guided cytology of groin lymph nodes in the management of squamous cell carcinoma of the vulva: a pilot study. British Journal of Obstetrics and Gynaecology 1999; 106: 863 –867. * 12. Hall TB, Barton DP, Trott PA et al. The role of ultrasound-guided cytology of groin lymph nodes in the management of squamous cell carcinoma of the vulva: 5-year experience in 44 patients. Clinical Radiology 2003; 58(5): 367– 371. 13. Steinkamp HJ, Cornehl M, Hosten N et al. Cervical lymphadenopathy: ratio of long- to short-axis diameter as a predictor of malignancy. British Journal of Radiology 1995; 68: 266–270. 14. Ahuja A, Ying M, Yang WT et al. The use of sonography in differentiating cervical lymphomatous lymph nodes from cervical metastatic lymph nodes. Clinical Radiology 1996; 51: 186 –190. 15. Ahuja A, Ying M, Yuen YH & Metreweli C. Power Doppler sonography of cervical lymphadenopathy. Clinical Radiology 2001; 56: 965–969. 16. Choi MY, Lee JW & Jang KJ. Distinction between benign and malignant causes of cervical, axillary, and inguinal lymphadenopathy: value of Doppler spectral waveform analysis. American Journal of Roentgenology 1995; 165: 981–984. 17. Voit C, Mayer T, Kron M et al. Efficacy of ultrasound B-scan compared with physical examination in followup of melanoma patients. Cancer 2001; 91: 2409–2416. 18. Tisnado J, Amendola MA, Walsh JW et al. Computed tomography of the perineum. AJR American Journal of Roentgenology 1981; 136: 475– 481. 19. Land R, Herod J, Moskovic E et al. Is there a role for routine CR scanning in the surgical management of primary squamous cell cancer of the vulval? Establishing an evidence base. International Journal of Gynecological Cancer 2002; 12: 664. abstract. 20. McCall AR, Olson MC & Potkul RK. The variation of inguinal lymph node depth in adult women and its importance in planning elective irradiation for vulvar cancer. Cancer 1995; 75: 2286–2288. * 21. Grey AC, Carrington BM, Hulse PA et al. Magnetic resonance appearance of normal inguinal nodes. Clinical Radiology 2000; 55: 124 –130. * 22. Vinnicombe SJ, Norman AR, Nicolson V & Husband JE. Normal pelvic lymph nodes: evaluation with CT after bipedal lymphangiography. Radiology 1995; 194: 349 –355. 23. Dorfman RE, Alpern MB, Gross BH & Sandler MA. Upper abdominal lymph nodes: criteria for normal size determined with CT. Radiology 1991; 180: 319–322. 24. Dooms GC, Hricak H, Moseley ME et al. Characterization of lymphadenopathy by magnetic resonance relaxation times: preliminary results. Radiology 1985; 155: 691 –697. 25. Hawnaur JM, Reynolds K, Wilson G et al. Identification of inguinal lymph node metastases from vulval carcinoma by magnetic resonance imaging: an initial report. Clinical Radiology 2002; 57: 995–1000. 26. Anzai Y & Prince MR. Iron oxide-enhanced MR lymphography: the evaluation of cervical lymph node metastases in head and neck cancer. Journal of Magnetic Resonance Imaging 1997; 7: 75–81. 27. Bellin MF, Roy C, Kinkel K et al. Lymph node metastases: safety and effectiveness of MR imaging with ultrasmall superparamagnetic iron oxide particles-initial clinical experience. Radiology 1998; 207: 799–808. * 28. Harisinghani MG, Saini S, Weissleder R et al. MR lymphangiography using ultrasmall superparamagnetic iron oxide in patients with primary abdominal and pelvic malignancies: radiographic-pathologic correlation. American Journal of Roentgenology 1999; 172: 1347– 1351. 29. Rockall AG, Sohaib SA, Barbar S et al. MR lymphography: comparison of signal characteristics on T2 and T2p weighted sequences with pathological correlation. Cancer Imaging 2002; 3: 19. 30. Bomanji JB, Costa DC & Ell PJ. Clinical role of positron emission tomography in oncology. Lancet Oncology 2001; 2: 157–164. 31. de Hullu JA, Pruim J, Que TH et al. Noninvasive detection of inguinofemoral lymph node metastases in squamous cell cancer of the vulva International. Journal of Gynaecolosical Cancer 1999; 9: 141 –146. 32. Cohn DE, Dehdashti F, Gibb RK et al. Prospective evaluation of positron emission tomography for the detection of groin node metastases from vulvar cancer. Gynecological Oncology 2002; 85: 179–184. * 33. Barton DPJ, Berman C, Cavanagh D et al. Lymphoscintigraphy in vulvar cancer: A pilot study. Gynecologic Oncology 1992; 46: 341–344. 34. deCesare SL, Fiorica JV, Roberts WS et al. A pilot study utilizing intraoperative lymphoscintigraphy for identification of the sentinel lymph nodes in vulvar cancer. Gynecologic Oncology 1997; 66: 425–428.
556 S. A. A. Sohaib and E. C. Moskovic * 35. DeCicco C, Sideri M, Bartolomei M et al. Sentinel node detection by lymphoscintigraphy and gamma detecting probe in patients with vulvar cancer. Journal of Nuclear Medicine 1997; 38: 33. 36. de Hullu JA, Hollema H, Piers DA et al. Sentinel lymph node procedure is highly accurate in squamous cell carcinoma of the vulva. Journal of Clinical Oncology 2000; 18: 2811–2816. 37. Tavares MGM, Sapienza MT, Galeb NA et al. The use of 99 mTc-phytate for sentinel node mapping in melanoma, breast cancer and vulvar cancer: a study of 100 cases. European Journal of Nuclear Medicine 2001; 28: 1597– 1604. 38. Chu J, Tamimi HK & Figge DC. Femoral node metastases with negative superficial inguinal nodes in early vulvar cancer. American Journal of Obstetrics and Gynecology 1981; 140: 337 –339. * 39. Stehman FB, Bundy BN, Dvoretsky PM & Creasman WT. Early stage I carcinoma of the vulva treated with ipsilateral superficial inguinal lymphadenectomy and modified radical hemivulvectomy: a prospective study of the Gynecologic Oncology Group. Obstetric and Gynecology 1992; 79: 490 –497.
2 Imaging in vulval cancer S. A. A. Sohaib*
BSc, MRCP, FRCR
Consultant Radiologist
E. C. Moskovic
FRCP, FRCR
Consultant Radiologist Department of Diagnostic Imaging, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
Cancer of the vulva spreads locally and, almost without exception, to the regional nodes in the groin to the superficial then deep inguinal groups and the pelvic nodes in a step-wise fashion. Because the single most important prognostic factor is the presence or absence of nodal disease, accurate diagnosis of nodal involvement is paramount. In the past, the status of inguinal nodes in vulval cancer has been ascertained only following groin node dissection, except in those cases with clinically obviously groin nodes. However, as up to 70% of patients at all stages of disease have negative nodes histologically, and as up to 70% of patients have groin or lower-limb problems after radical groin surgery, this approach incurs ‘unnecessary’ surgery for the majority of patients with the attendant morbidity. Using new diagnostic imaging methods, detection and assessment of groin lymph nodes has been developing over the past few years with the ultimate intention of reducing groin node surgery in node-negative patients. In this chapter we review the role of imaging in patients with vulval cancer in which there is a greater role in the assessment of nodal disease rather than in the assessment of the cancer on the vulva. Key words: vulval cancer; lymph node; ultrasound; magnetic resonance imaging.
Vulval cancer is an uncommon gynaecological malignancy, affecting mainly the elderly. Women with vulval carcinoma are assessed clinically with examination of the vulva and the groin, and this may involve an examination under anaesthesia. Full-thickness biopsy(s) of the lesion is important to confirm the diagnosis and to determine the extent of the lesion. The most important prognostic factors include size of the primary lesion and involvement of the regional lymph nodes. Both of these features are incorporated into the FIGO staging of the tumour (see Table 1).1,2 The standard treatment for several decades had been radical vulvectomy with bilateral inguinofemoral lymphadenectomy. This radical approach had significant morbidity.3 There has now been a trend to a more conservative surgical approach to both the vulval and the groin phase.3 The purpose of radical groin lymphadenectomy is for diagnostic and therapeutic benefit. Doubt remains about the therapeutic role, especially in node-negative patients. Diagnostic imaging techniques may be used in the detection * Corresponding author. Tel.: þ44-207-808-2343; Fax: 44-207-352-0726. E-mail address: [email protected] (S. A. A. Sohaib). 1521-6934/$ - see front matter Q 2003 Elsevier Ltd. All rights reserved.
544 S. A. A. Sohaib and E. C. Moskovic
Table 1. Staging of the carcinoma of the vulva.1,2 T1 T2 T3 T4 N0 N1 N2 M0 M1
Tumour less than 2 cm in the greatest dimension and confined to vulva or perineum Tumour more than 2 cm in the greatest dimension and confined to the vulva or perineum Tumour invading any of the following: lower urethra, vagina or anus Tumour invading any of the following: upper urethra, bladder mucosa, rectal mucosa, and pelvic bone No regional lymph node metastasis Unilateral lymph node metastasis Bilateral lymph node metastasis No distant metastasis Distant metastasis (including pelvic lymph nodes metastasis)
FIGO Stage Grouping T1, N0, M0 T2, N0, M0 T1 or T2, N1, M0 T3, N0 or N1, M0 IVA T1 or T2 or T3, N2, M0 T4, any N, M0 IVB Any T, any N, M1 I II III
and assessment of groin lymph nodes for metastatic disease with the intention of reducing groin-node surgery.
PRIMARY VULVAL CANCER Cancer of the vulva involves the labia in about two-thirds of patients, with other sites involved in the remaining third.3 Vulval cancer usually spreads slowly and infiltrates local tissues before involving the lymph nodes in the groin. Local spread can extend to involve the vagina, urethra and anus and rarely to the urethra, bladder and bone. In more advanced cases the pelvic nodes can be affected. Disease outside the pelvis is rare in vulval cancer with the exception of malignant melanoma and rare sarcomas. Imaging techniques have had a relatively limited role in the assessment of the primary tumour as this is readily assessed clinically, especially as small lesions are often not identified with imaging. However, magnetic resonance imaging (MRI) has been shown to identify primary vulval cancer accurately4 (Figures 1 and 2). When the tumour is seen on MRI the extent of tumour can also be outlined. Most tumours show a typical signal intensity pattern of low signal intensity on T1-weighted images and moderate to high signal intensity on T2-weighted images. We have also found that intravenous gadolinium was not helpful in the identification of the primary lesion, and small primary tumours and tumours that were not thick (i.e. plaque-like lesions) were not seen.4 This may have been due to the fact that the imaging parameters were not optimal for the identification of small primary lesions in this retrospective study. Using high-resolution imaging with a small field of view and thinner sections may have identified more primary lesions. MR imaging is likely to be of more benefit in the assessment of more locally advanced disease as the multi-planar imaging capability may be helpful in assessing involvement of other pelvic organs. Using optimal MR imaging techniques, deep extension of the primary
Imaging in Vulval cancer 545
Figure 1. MRI of carcinoma of vulva. Axial T2-weighted fast spin-echo MR image shows 3-cm tumour (arrow) arising from right labia.
Figure 2. MRI of a large central carcinoma of vulva (straight arrow) involving clitoris (curved arrow). Axial T2-weighted fast spin-echo MR image shows intermediate-signal-intensity tumour extending up to involve clitoris.
546 S. A. A. Sohaib and E. C. Moskovic
tumour and assessment of adjacent pelvic structures (e.g. anal sphincter) may be better assessed by MR imaging than clinical examination but this requires further study.
LYMPH NODE SPREAD Lymphatic drainage of the vulva is to the inguinal and femoral nodes in the groin. The superficial inguinal nodes are just below the skin along the medial two-thirds of the inguinal ligament and along the saphenous vein close to the sapheno –femoral junction. The inguinal nodes are the primary nodes which drain the vulva, and these, in turn, drain into the deep femoral nodes located along the femoral artery and vein. From there the lymphatic drainage is to the external iliac lymph nodes, the lowest of which is at the entrance of the femoral canal; it is known as the Cloquet node and is an important indicator of the likelihood of metastatic spread to the pelvic nodes. Drainage from the midline structures, such as the perineum and clitoris, is to both groins, and there is some contralateral drainage from other parts of the vulva (large Bartholin cancer). A truly lateral vulval cancer spreads to the ipsilateral regional nodes.5 Pelvic node involvement is uncommon and is secondary to groin node involvement. For central vulval cancers there is very rarely direct spread to the pelvic nodes via the internal pudendal vessels. Complete obstruction of the lymphatics can lead to involvement of the subcutaneous and dermal lymphatics of the vulva, upper thigh and lower abdomen. The status of the groin node spread is the important prognostic marker. Patients with negative groin nodes have an approximately 90% survival whereas patients with positive nodes have a survival of approximately 50%.6 In the past, the status of clinically non-suspicious inguinal nodes in vulval cancer has been ascertained only following groin node dissection. However, as up to 70% of patients at all stages of disease have negative nodes, this approach incurs unnecessary surgery with the attendant morbidity for the majority of patients.3 Clinical palpation is usually restricted to the superficial nodes, and, as a method for detecting groin lymph node metastases, it is unreliable, with a sensitivity of 57% and a specificity of 62%.7 Modern diagnostic imaging, however, is increasingly capable of detecting whether a lymph node contains metastatic disease with a sensitivity and specificity that make them potentially very useful clinically.
RECURRENT DISEASE Most recurrent vulval cancers arise in the vulva, or groins. In some patients the recurrence is in the skin bridge—the tissue between the vulval and groin incisions; in other patients there may be pelvic nodal metastases. Disease outside the pelvis is rare except for the less common vulval cancers, including malignant melanoma. Commonly the recurrence is easily assessed clinically, although in some patients a formal examination under anaesthesia may be necessary. Exclusion of pelvic or more distant disease (including chest metastases) is important before radical treatment is undertaken. For deep-seated recurrences, for example from Bartholin gland carcinoma, or angiosarcoma, either Computed tomography (CT) or MRI can be useful in assessing the extent of disease, and whether, for example, there is bone involvement. Extension of disease to the anal canal, urethra or bladder is best determined by thorough clinical assessment and biopsies.
Imaging in Vulval cancer 547
ASSESSMENT OF RADIOLOGICAL IMAGING TECHNIQUES Ultrasound (USS) The advent of high-resolution, high-frequency (7– 15 MHz) ultrasound has proved extremely useful in the evaluation of regional lymph nodes for metastatic disease, although not all authors agree.8 – 10 This technique allows detection of nodes as small as 5 mm within the superficial soft tissues and facilitates fine-needle aspiration for cytology (FNAC). Ultrasound evaluation of lymph nodes is now used routinely in staging head and neck tumours, melanoma and some breast cancers and has recently been applied, with fine-needle aspiration cytology (FNAC), to compliment staging of vulval cancer with a high level of sensitivity and specificity.11,12 On ultrasound, normal nodes (Figure 3) are oval in shape and have an echogenic hilus with a hypoechoic lymphoid cortex. A fatty node may be isoechoic with the surrounding fatty stroma. Normal lymph nodes are typically under 1 cm in diameter but this can be variable, with benign reactive nodes as large, i.e. 2 – 3 cm. Lymph nodes with metastatic disease (Figure 4) tend to develop a rounded shape, and a ratio of long/short axis diameter of the node of less than 2 is taken to indicate malignancy.13,14 Other useful sonographic features are loss of the echogenic hilar sinus fat, irregular margin and increasing low attenuation of the cortex.11 Doppler evaluation on ultrasound can further aid in the characterization of lymph nodes. Colour and power Doppler pattern in metastatic nodes demonstrate more peripheral vascularity than reactive nodes, which have more hilar perfusion. This relates
Figure 3. Ultrasound of normal node with oval contour, peripheral low attenuation lymphoid tissue and higher attenuation central medullary sinus tissue.
548 S. A. A. Sohaib and E. C. Moskovic
Figure 4. Ultrasound of metastatic lymph node. The node is large and rounded with internal heterogeneity.
to the abnormal distribution of vessels within malignant nodes, with peripheral foci of tumour causing neovascularity locally within the marginal and medullary sinuses.15 Spectral waveform analysis may also be used to distinguish benign from malignant nodes, nodes with high resistive index being almost always involved by tumour.16 Ultrasound assessment of lymph nodes can be combined with FNAC. Ultrasound can be used to guide the cytological assessment of suspicious nodes (Figure 5). The technique is carried out under local anaesthetic, and aspiration using a 21G needle is performed with real-time ultrasound guidance. In the original report on these techniques using morphological criteria, a sensitivity of 85% and a specificity of 83% were reported.11 Cytology of groin nodes had a specificity 100% but a sensitivity of only 58% owing to a high false-negative rate from sampling error.11 Recently, data suggest that the combination of ultrasound-guided FNAC of nodes considered suspicious on ultrasound criteria has a sensitivity and specificity approaching 100% for the detection of metastatic disease12 (see Table 2). There are, however, a number of limitations with ultrasound and cytology. First, there is a learning curve for the technique—but this can be overcome with training and experience. Second, there is a diagnostic overlap in the appearance of benign reactive and metastatic nodes. Third, a lymph node may appear abnormal and contain metastatic disease but the aspirate fails to obtain abnormal cells. This relates to sampling error and can be difficult to overcome in a small node where placement of the needle is exacting. Lastly, small-volume micrometastases within lymph nodes deemed normal on ultrasound criteria remain a diagnostic challenge because they are beyond the resolution of current technology. However, routine histological sampling of lymph
Imaging in Vulval cancer 549
Figure 5. Aspiration needle (arrow) in situ in a metastatic lymph node during fine-needle aspiration for cytology (FNAC) procedures.
nodes will also not detect micro-metastasis, except by chance in a random section, as only a small volume of the lymph node is actually examined microscopically. In patients who are being monitored serially using ultrasound, a follow-up scan at 2 –3 months will detect nodes as they enlarge and become sonographically abnormal. It is already our practice in patients who have been unsuitable for, or reluctant to have, groin node surgery following the diagnosis of early-stage vulval carcinoma, to undertake initial groin node ultrasound with FNAC. If the groin nodes are sonographically and cytologically benign, then 3-monthly ultrasound is undertaken, with FNAC only if the nodes become suspicious on ultrasound criteria. Indeed, in malignant melanoma, USS has been used as a means of nodal surveillance.17 We plan to embark on a randomized controlled trial on the use of groin USS/FNAC in the management of the groin nodes in primary squamous-cell cancer of the vulva. Table 2. Lymph node assessment.
Ultrasound Cytology Combined
Sensitivity (95% CI)
Specificity (95% CI)
86 (67–96) 75 (55–89) 93 (76–99)
96 (85–99) 100 (92–100) 100 (92–100)
Reproduced from Hall TB, et al (2003, Clinical Radiology, in press) with permission.
550 S. A. A. Sohaib and E. C. Moskovic
CT scanning in vulval cancer Computed tomography (CT) has been used in the radiological imaging of all gynaecological cancers; it has the least impact on the clinical management of vulval cancer. There were some early reports about its usefulness in assessing pelvic anatomy.18 Its role has been superseded to some extent by MRI—in which there is the facility to reconstruct sagittal and coronal images. It may still have a place in the assessment of rare vulval cancers such as the angiosarcoma, but it is inferior to clinical examination. In a recent review of the use of CT scanning in our institution, we found that it did not contribute to clinical management and, as a result, we no longer routinely use CT scanning in patients with vulval cancer.19
Magnetic resonance imaging (MRI) MRI has a number of advantages for evaluating lymph nodes. Vessels and lymph nodes can be differentiated without the use of intravenous contrast media, and its superior contrast resolution permits the detection of small nodes. On MR the cross-sectional images also allow assessment of the depth of the nodes from the skin surface, which can vary markedly depending of the patient’s body habitus.20,21 This information could be invaluable in the planning of external beam radiotherapy. Furthermore, MR images allow for precise anatomical localization of abnormal lymph nodes—which may help in surgical planning. On MRI it is possible to identify three inguinal node groups.21 The proximal superficial group of nodes lies superficial to the inguinal ligament and above the level of the sapheno – femoral junction. The distal superficial group lies superficial to the inguinal ligament and at or below the level of the sapheno – femoral junction. The deep ingiuinal nodes are sited deeply medial to the common femoral vein at or cranial to the sapheno – femoral junction.21 Groin lymph nodes can be detected easily on MRI (Figure 6). In cross-sectional imaging techniques, size has been the main criterion for distinguishing between benign and malignant lymph nodes. There is agreement that measurement of the maximum short axis diameter is a more reliable criterion than the maximum long axis diameter.22, 23 The number and size of lymph nodes on MRI varies considerably.21 The sensitivity and specificity of detecting abnormal lymph nodes depends on the threshold used to categorize normal from abnormal nodes. Using a size criterion of abnormality of 10 mm or greater in short-axis diameter for superficial inguinal nodes, the reported sensitivity for detection of malignant nodes was 40% and the specificity 97%.4 For deep inguinal nodes, if nodes 8 mm or greater in short-axis diameter are considered abnormal then the sensitivity for detection of malignant nodes was 50% and the specificity 100%.4 The use of these size criteria of abnormal lymph nodes gives a high specificity but low sensitivity. A test with high specificity would have few false negatives and therefore if a node were enlarged the surgeon would have a high degree of confidence that the lymph node was involved. Therefore, if the patient was a poor-risk candidate for surgery then arguably non-surgical therapy could be used. Other investigators have tried to use other criteria on imaging to distinguish benign from malignant nodes. We did not find the number of lymph nodes in the groin useful in determining affected from unaffected groins. Signal intensity or T1 and T2 relaxation times has not been found to be useful in distinguishing between benign and malignant nodes.24
Imaging in Vulval cancer 551
Figure 6. Two metastatic lymph nodes in the left groin seen on (A) axial T2-weighted fast spin-echo MR image and on (B) left groin ultrasound.
552 S. A. A. Sohaib and E. C. Moskovic
In another MR study using high-resolution imaging with surface coil; the criteria considered suspicious for malignancy were (i) long-axis diameter greater than 21 mm, (ii) short-axis diameter greater than 10 mm, (iii) long-to-short axis ratio less than 1.3:1, and (iv) irregularity of contour and cystic change within solid parts of a lymph node.25 The most useful observations on MRI for identifying metastatic lymph nodes were contour irregularity and cystic change. MR imaging can be compared with other cross-sectional imaging techniques, i.e. ultrasound and computed tomography (CT). CTevaluation of lymph nodes is similar to that with MRI, with size criteria used to identify abnormal nodes. Ultrasound is cheaper and more readily available than MRI and it can be easily used to guide FNAC. The need for a relatively long examination by a skilled radiologist or sonographer is a disadvantage over the MRI technique. An unsupervized radiographer can routinely run the MR protocol, the images subsequently being read by any radiologist familiar with the criteria used. MR images are also more reproducible for comparison with baseline studies when looking for change in lymph node size or morphology that might indicate the development of metastases. It would remain possible to use ultrasound-guided biopsy to sample any equivocal lymph node given that the relationship of the lymph node to the vessels is clearly depicted on MRI. Finally, not all patients can undergo an MRI scan because of fear, and cardiac pacemakers, for example. MR lymphography More recently ultra-small-iron-oxide-particle (USIOP) has become available for MR lymphography.26 – 28 These are iron oxide nano-particles (20 nm) coated with lowmolecular-weight dextran. The generic name for this agent is feruxtram; it is marketed in Europe under the name of Sinerem and in the USA as Comibdex. USIOP is administered intravenously. The iron oxide particles are taken up by the macrophages of the lymph nodes, where they accumulate. They reduce the signal intensity of normally functioning nodes on post-contrast T2- and T2p-weighted images through the magnetic susceptibility effects of iron oxide. Lymph nodes with metastatic disease, in which macrophages are replaced by tumour cells, do not accumulate the iron oxide and therefore show no significant change in signal intensity on post-contrast T2- and T2pweighted images. Early clinical experience suggests that USIOP-enhanced MR lymphography improves the sensitivity and specificity for the detection of nodal metastases and suggests that micro-metastases could be detected in normal-sized nodes.27 Larger studies in a number of centres in Europe and the USA are currently ongoing. Our early experience with MR lymphography in pelvic malignancy has shown that, compared to the conventional MR imaging criterion, i.e. lymph node size, MR lymphography is more sensitive at detecting involved lymph nodes.29 The sensitivity was improved from 55 to 89% while specificity was 89%.29 Positron emission tomography (PET) PET with 18F-FDG has been used as a functional method of determining tumour viability in several cancers.30 This method is based on the increased cellular glucose uptake that is associated with malignancy. PET has also been investigated in the evaluation of groin nodes in vulval cancer.31,32 A study in 15 patients, using the tracer 18-fluorodeoxyglucose, showed that PET imaging was relatively insensitive in predicting lymph node metastasis, it had a sensitivity of 67%, a specificity of 95%, a positive predictive value of 86% and a negative predictive value of 86%.32 PETwas more accurate
Imaging in Vulval cancer 553
in detecting extranodal metastases than disease confined within the groin nodes.32 A further PET study in 25 patients, with L-[1-11C]-tyrosine (TYR) as tracer, showed that, in the detection of inguino-femoral lymph node metastases, PET was not superior to palpation.31 The sensitivity, specificity, accuracy and positive and negative predictive values for TYR-PET were, respectively, 53, 95, 94, 33 and 98% per lymph node and 75, 62, 65, 41 and 88 per groin.31 The technique is still being evaluated and may not be a practical affordable option. Lymphoscintigraphy—imaging for sentinel lymph node biopsy The concept of excision and histological assessment of the sentinel node in vulval cancer—to decrease the morbidity associated with groin dissection—has become a topic of interest in gynaecological oncology.33 – 37 The sentinel node is defined as the first node in the lymphatic chain or basin that receives primary lymphatic flow from the suspected lesion. This node is used as a representative of the entire lymph node basin and, in theory, is the first site of metastatic disease in a lymph node. If the sentinel node is negative for metastatic disease the remainder of the nodes should also be free of tumour, thereby avoiding unnecessary surgery. Lymphoscintigraphy in vulval cancer—which was first described in a pilot study to test the feasibility of the technique—was not used to detect metastatic disease in lymph nodes or to identify the sentinel node.33 Various techniques have been described. The radioactive tracer commonly used is technetium 99 m (Tc-99 m) which is usually linked to sulphur colloid or to human albumin; however, other tracers—such phytate—have been used.37 The radioactive tracer is injected intra-lesionally or peri-lesionally. Imaging can be performed pre-operatively and/or intra-operatively using hand-held gamma probes to identify the nodes that have taken up the radioactive tracer. Lymphoscintigraphy may also be combined with the blue-dye technique for identifying sentinel nodes.36 The major advantage of using the sentinel node approach in early vulval cancer is to decrease the associated morbidity of groin dissection. However, there are major drawbacks. First, there is no evidence to suggest that superficial inguinal node dissection alone results in a decreased incidence of lymphoedema as compared with complete lymphadenectomy. Second, metastasis to the deep inguinal or femoral nodes has been found without evidence of superficial node disease.38 A GOG study revealed a high incidence of groin recurrence after performing only superficial groin dissection, and this modification of groin node dissection is no longer recommended.39 Other drawbacks to sentinel node biopsy include the need for operator experience; moreover, logistically, performing the procedures can be demanding, with the need for co-ordination of the patient between different departments.
SUMMARY Imaging has a limited role in the evaluation of primary site of disease in vulval cancer as this is readily assessed clinically. For larger cancers MR imaging may be helpful in evaluating the extent of disease in patients with advanced tumour involving the perineum, vagina and anal canal. Groin lymphadenectomy is performed for diagnostic and therapeutic reasons, and groin node status is the most important prognostic factor. Clinical palpation is unreliable, but a number of diagnostic imaging techniques may be of value in detecting metastases with the aim of permitting a more conservative approach
554 S. A. A. Sohaib and E. C. Moskovic
to the management of groin nodes. Ultrasound combined with FNAC offers a quick and easy method and is a highly specific method for identifying involved lymph nodes. New MR imaging techniques and MR lymphography requires further evaluation. Sentinel node biopsy offers another exciting possibility.
ACKNOWLEDGEMENTS We would like to thank Mrs Janet MacDonald for assistance with the illustrations.
Practice points † primary tumour is best assessed clinically. For advanced tumours, deep extension of the primary tumour, and assessment of adjacent pelvic structures (e.g. anal sphincter) clinical assessment may be supplemented with MR imaging † the disease status of the regional groin lymph nodes is the most important prognostic factor in vulval cancer. Hence, this influences the decision to perform radical of conservative treatment † combined ultrasound and FNAC provide sensitive and specific tools for preoperative assessment and may prevent unnecessary groin dissection and attendant morbidity in selected patients with vulval cancer
Research agenda † outcome of patients selected for conservative treatment following combined ultrasound and FNAC † use of MR lymphography in vulval cancer † validation of sentinel lymph node biopsy in vulval cancer in a large multi-centre trail † outcome of patients selected for conservative or radical surgery following sentinel lymph node biospy
REFERENCES 1. International Union Against Cancer [UICC]: TNM classification of malignant tumours, 5th edn. New York: Wiley-Liss, 1997. 2. Benedet JL, Bender H, Jones Jr. H et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. International Journal of Gynaecology and Obstetrics 2000; 70: 209 –262. * 3. Cavanagh D & Hoffman MS. Controversies in the management of vulvar carcinoma. British Journal of Obstetrics and Gynaecology 1996; 103: 293–300. * 4. Sohaib SA, Richards PS, Ind Tet al. MR imaging of carcinoma of the vulva. American Journal of Roentgenology 2002; 178: 373–377. 5. Iversen T & Aas M. Lymphatics of the vulva. British Journal of Obstetrics & Gynaecology 1963; 70: 751–765. 6. Ghurani GB & Penalver MA. An update on vulvar cancer. American Journal of Obstetrics and Gynecology 2001; 185: 294 –299. 7. Piura B, Rabinovich A, Cohen Yet al. Squamous cell carcinoma of the vulva in the south of Israel: a study of 50 cases. Journal of Surgical Oncology 1998; 67: 174–181.
Imaging in Vulval cancer 555 8. Makela PJ, Leminen A, Kaariainen M & Lehtovirta P. Pretreatment sonographic evaluation of inguinal lymh nodes in patients with vulval malignancy. Journal of Ultrasound Medicine 1993; 5: 255–258. 9. Dragoni F, Cartoni C, Pescarmona E et al. The role of high resolution pulsed and color Doppler ultrasound in the differential diagnosis of benign and malignant lymphadenectomy. Cancer 1999; 85: 2485– 2490. 10. Abang Mohammed DK, Uberoi R, de B Lopes A & Monaghan JM. Inguinal node status by ultrasound in vulvar cancer. Gynecologic Oncology 2000; 77: 825–830. * 11. Moskovic EC, Shepherd JH, Barton DP et al. The role of high resolution ultrasound with guided cytology of groin lymph nodes in the management of squamous cell carcinoma of the vulva: a pilot study. British Journal of Obstetrics and Gynaecology 1999; 106: 863 –867. * 12. Hall TB, Barton DP, Trott PA et al. The role of ultrasound-guided cytology of groin lymph nodes in the management of squamous cell carcinoma of the vulva: 5-year experience in 44 patients. Clinical Radiology 2003; 58(5): 367– 371. 13. Steinkamp HJ, Cornehl M, Hosten N et al. Cervical lymphadenopathy: ratio of long- to short-axis diameter as a predictor of malignancy. British Journal of Radiology 1995; 68: 266–270. 14. Ahuja A, Ying M, Yang WT et al. The use of sonography in differentiating cervical lymphomatous lymph nodes from cervical metastatic lymph nodes. Clinical Radiology 1996; 51: 186 –190. 15. Ahuja A, Ying M, Yuen YH & Metreweli C. Power Doppler sonography of cervical lymphadenopathy. Clinical Radiology 2001; 56: 965–969. 16. Choi MY, Lee JW & Jang KJ. Distinction between benign and malignant causes of cervical, axillary, and inguinal lymphadenopathy: value of Doppler spectral waveform analysis. American Journal of Roentgenology 1995; 165: 981–984. 17. Voit C, Mayer T, Kron M et al. Efficacy of ultrasound B-scan compared with physical examination in followup of melanoma patients. Cancer 2001; 91: 2409–2416. 18. Tisnado J, Amendola MA, Walsh JW et al. Computed tomography of the perineum. AJR American Journal of Roentgenology 1981; 136: 475– 481. 19. Land R, Herod J, Moskovic E et al. Is there a role for routine CR scanning in the surgical management of primary squamous cell cancer of the vulval? Establishing an evidence base. International Journal of Gynecological Cancer 2002; 12: 664. abstract. 20. McCall AR, Olson MC & Potkul RK. The variation of inguinal lymph node depth in adult women and its importance in planning elective irradiation for vulvar cancer. Cancer 1995; 75: 2286–2288. * 21. Grey AC, Carrington BM, Hulse PA et al. Magnetic resonance appearance of normal inguinal nodes. Clinical Radiology 2000; 55: 124 –130. * 22. Vinnicombe SJ, Norman AR, Nicolson V & Husband JE. Normal pelvic lymph nodes: evaluation with CT after bipedal lymphangiography. Radiology 1995; 194: 349 –355. 23. Dorfman RE, Alpern MB, Gross BH & Sandler MA. Upper abdominal lymph nodes: criteria for normal size determined with CT. Radiology 1991; 180: 319–322. 24. Dooms GC, Hricak H, Moseley ME et al. Characterization of lymphadenopathy by magnetic resonance relaxation times: preliminary results. Radiology 1985; 155: 691 –697. 25. Hawnaur JM, Reynolds K, Wilson G et al. Identification of inguinal lymph node metastases from vulval carcinoma by magnetic resonance imaging: an initial report. Clinical Radiology 2002; 57: 995–1000. 26. Anzai Y & Prince MR. Iron oxide-enhanced MR lymphography: the evaluation of cervical lymph node metastases in head and neck cancer. Journal of Magnetic Resonance Imaging 1997; 7: 75–81. 27. Bellin MF, Roy C, Kinkel K et al. Lymph node metastases: safety and effectiveness of MR imaging with ultrasmall superparamagnetic iron oxide particles-initial clinical experience. Radiology 1998; 207: 799–808. * 28. Harisinghani MG, Saini S, Weissleder R et al. MR lymphangiography using ultrasmall superparamagnetic iron oxide in patients with primary abdominal and pelvic malignancies: radiographic-pathologic correlation. American Journal of Roentgenology 1999; 172: 1347– 1351. 29. Rockall AG, Sohaib SA, Barbar S et al. MR lymphography: comparison of signal characteristics on T2 and T2p weighted sequences with pathological correlation. Cancer Imaging 2002; 3: 19. 30. Bomanji JB, Costa DC & Ell PJ. Clinical role of positron emission tomography in oncology. Lancet Oncology 2001; 2: 157–164. 31. de Hullu JA, Pruim J, Que TH et al. Noninvasive detection of inguinofemoral lymph node metastases in squamous cell cancer of the vulva International. Journal of Gynaecolosical Cancer 1999; 9: 141 –146. 32. Cohn DE, Dehdashti F, Gibb RK et al. Prospective evaluation of positron emission tomography for the detection of groin node metastases from vulvar cancer. Gynecological Oncology 2002; 85: 179–184. * 33. Barton DPJ, Berman C, Cavanagh D et al. Lymphoscintigraphy in vulvar cancer: A pilot study. Gynecologic Oncology 1992; 46: 341–344. 34. deCesare SL, Fiorica JV, Roberts WS et al. A pilot study utilizing intraoperative lymphoscintigraphy for identification of the sentinel lymph nodes in vulvar cancer. Gynecologic Oncology 1997; 66: 425–428.
556 S. A. A. Sohaib and E. C. Moskovic * 35. DeCicco C, Sideri M, Bartolomei M et al. Sentinel node detection by lymphoscintigraphy and gamma detecting probe in patients with vulvar cancer. Journal of Nuclear Medicine 1997; 38: 33. 36. de Hullu JA, Hollema H, Piers DA et al. Sentinel lymph node procedure is highly accurate in squamous cell carcinoma of the vulva. Journal of Clinical Oncology 2000; 18: 2811–2816. 37. Tavares MGM, Sapienza MT, Galeb NA et al. The use of 99 mTc-phytate for sentinel node mapping in melanoma, breast cancer and vulvar cancer: a study of 100 cases. European Journal of Nuclear Medicine 2001; 28: 1597– 1604. 38. Chu J, Tamimi HK & Figge DC. Femoral node metastases with negative superficial inguinal nodes in early vulvar cancer. American Journal of Obstetrics and Gynecology 1981; 140: 337 –339. * 39. Stehman FB, Bundy BN, Dvoretsky PM & Creasman WT. Early stage I carcinoma of the vulva treated with ipsilateral superficial inguinal lymphadenectomy and modified radical hemivulvectomy: a prospective study of the Gynecologic Oncology Group. Obstetric and Gynecology 1992; 79: 490 –497.