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Selective Inguinal Lymphadenectomy in the Treatment of Invasive Squamous Cell Carcinoma of the Vulva

Selective Inguinal Lymphadenectomy in the Treatment of Invasive Squamous Cell Carcinoma of the Vulva Hindawi Publishing Corporation International Journal of Surgical Oncology Volume 2011, Article ID 284374, 6 pages doi:10.1155/2011/284374 Review Article Selective Inguinal Lymphadenectomy in the Treatment of Invasive Squamous Cell Carcinoma of the Vulva Christopher P. DeSimone, Jeffrey Elder, and John R. van Nagell Jr. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center- Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA Correspondence should be addressed to Christopher P. DeSimone, cpdesi00@uky.edu Received 6 January 2011; Accepted 5 April 2011 Academic Editor: E. W. Martin Copyright © 2011 Christopher P. DeSimone et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. En bloc radical vulvectomy with bilateral inguinofemoral lymphadenectomy has now been replaced by radical wide excision and selective inguinal lymphadenectomy based on the stage and location of invasive vulvar cancer. Early stage lateral cancers can be effectively treated by radical wide excision and ipsilateral superficial inguinal lymphadenectomy. Lymph node mapping using perilesional injection of radiocolloid and blue dye may identify sentinel lymph nodes which can be removed, thereby avoiding the morbidity of full inguinal lymphadenectomy in selected patients with early stage disease. 1. Introduction the contralateral inguinal lymph nodes if there is no evidence of ipsilateral lymph node metastases. Likewise, it is unusual Although squamous cell carcinoma of the vulva is not com- for the deep inguinal nodes (below the cribriform fascia) to mon, it is occurring with increasing frequency in younger be involved in the absence of superficial inguinal lymph node women, particularly in those exposed to human papilloma spread. The current International Federation of Gynecology virus (HPV). With efforts at education, many patients are and ObstetricsStaging System forvulvarcancerisnow based presenting with early stage disease which is amenable to on surgical findings as illustrated in Table 1 and reflects the surgery. This year, there will be approximately 3500 new extent and location of inguinal lymph node metastases. casesofvulvarcancerinthe United States, representing 5% of all gynecologic cancers [1]. The surgical management of 3. Surgery of the Primary Vulvar Lesion this disease has evolved from en bloc resection of the entire vulva with bilateral superficial and deep inguinofemoral lym- The Basset-Way operation which was the standard of care phadenectomy to a more conservative approach involving in the operative management of patients with vulvar cancer radical wide excision of the primary lesion and specific included the en bloc resection of the primary lesion and types of inguinal lymphadenectomy based on the stage and surrounding vulvarskinaswell asthe skin over both groins anatomic location of disease. (Figure 2(a))[4]. Although this procedure was curative in the majority of cases, the wound defect was significant and incisional breakdown and lymphedema of both lower 2. Anatomic Pathways of Spread and Staging extremities were common. Currently, the surgical treatment The lymphatic drainage of the vulva has been studied of vulvar cancer involves radical wide excision of the primary extensively and described in numerous publications [2, 3]. lesion and inguinal lymphadenectomy through separate Generally, lateralizing lesions (>1cm beyond the midline) groin incisions (Figure 2(b))[5]. Heaps and colleagues [6] drain to the ipsilateral superficial inguinal lymph nodes, reported that local control of vulvar cancers could be whereas midline lesions can drain to either side (Figure 1). achieved in 100% of cases provided that a 1 cm margin of It is extremely rare for lateralizing vulvar cancers to spread to normal skin was included in the surgical specimen. These 2 International Journal of Surgical Oncology (a) (b) Figure 1: Lateral vulvar lesions >1 cm from the midline (a) spread initially to the ipsilateral superficial inguinal lymph nodes, whereas midline lesions can spread to both groins (b). (a) (b) Figure 2: The Bassett-Way operation includes en bloc radical resection of the primary lesion and surrounding vulvar skin as well as the skin over both groins (a). Radical wide excision of the vulvar cancer includes a margin of at least 1 cm of normal skin around the entire lesion. Inguinal lymphadenectomy is performed through separate groin incisions (b). observations were confirmed by De Hullu and coworkers [7] a method to identify regional lymph node metastases in who reported that there was no local recurrence of T or breast cancer [12, 13] and cutaneous melanoma [4]and has T vulvar cancers when a margin of at least 8 mm normal now been evaluated in patients with early stage vulvar cancer. skin was excised with the primary lesion. In contrast, patients Specifically, 1-2 mCi of radiocolloid is injected intradermally with a margin of <8 mm had a local recurrence rate of 22%. around the lesion (Figure 3), and a hand held gamma At present, it is recommended that a margin of at least 1 cm detection device is used to identify the sentinel lymph of normal skin around the circumference of the primary node(s). Recently, lymphoscintigraphy has been combined vulvar lesion be included in the surgical specimen and that with intraoperative perilesional injection of isosulfan blue the underlying subcutaneous tissue be removed to the level as a method to identify sentinel nodes in the inguinal area. of the perineal fascia. Inguinal lymphadenectomy is then Localization of the sentinel node(s) is usually apparent 5–15 performed through separate incisions. minutes after injection of blue dye and 30 minutes after injec- tion of radiocolloid. Selman and colleagues [14] performed a systematic review of the accuracy of sentinel lymph node 4. Sentinel Lymphadenectomy detection in identifying inguinal lymph node metastases in Sentinel lymph node excision is now being recommended in vulvar cancer and reported that the combination of 99 mTc selected patients with early stage squamous cell carcinoma radiocolloid and isosulfan blue dye successfully detected as a means to avoid the operative morbidity associated with sentinel lymph nodes in 97% of cases. It also had a negative inguinofemoral lymphadenectomy [8–10]. It is estimated predictive value (NPV) of 99.1%. Further analysis has that only 25–30% of patients with early stage vulvar cancer indicated that sentinel lymph node mapping is most accurate have lymph node metastases, and complete inguinofemoral in patients with early stage lateral vulvar cancers [15]. lymphadenectomy is associated with postoperative wound A persisting concern about sentinel lymph node mapping complications and lower extremity edema in 30–40% of in vulvar cancer is the frequency of groin recurrences in patients [11]. Sentinel lymph node mapping using radio- patients with negative sentinel lymph nodes. In a multi- labelled ultrafiltered sulfur colloid was initially reported as institutional observational study, Van Der Zee and coworkers International Journal of Surgical Oncology 3 Table 1: FIGO staging of invasive cancer of the vulva. of patients having sentinel node excision were significantly reduced when compared to that of women undergoing Stage I Tumor confined to the vulva complete inguinofemoral lymphadenectomy. These authors Lesions ≤2 cm in size confined to the vulva or concluded that sentinel node dissection, performed by a IA perineum and with stromal invasion ≤1.0 mm , quality-controlled multidisciplinary team, should be offered no nodal metastasis to selected patients with early stage vulvar cancer as a Lesions >2 cm in size confined to the vulva or means to avoid the postoperative morbidity associated with IB perineum with stromal invasion greater than 1.0 mm , inguinofemoral lymphadenectomy. no nodal metastasis There is a definite learning curve in the performance Tumor of any size with extension to adjacent perineal and interpretation of lymph node mapping, and it is Stage II structures (1/3 lower urethra, 1/3 lower vagina, anus), recommended that a multidisciplinary group within each no nodal metastasis institution perform sentinel node mapping in at least 10– Tumor of any size with or without extension to adjacent 20 cases before it becomes an accepted procedure [10, 16]. Stage III perineal structures (1/3 lower urethra, 1/3 lower vagina, If sentinel lymph nodes cannot be identified by mapping or anus) with positive inguinofemoral lymph nodes if there is uncertainty concerning interpretation of findings, a IIIA With 1 lymph node metastasis (≥5 mm), superficial inguinal lymphadenectomy should be performed. (i) With 2 or more lymph node metastases (≥5 mm), Patients with a positive sentinel node should undergo a IIIB (ii) 3 or more lymph node metastases (<5 mm) full inguinofemoral lymphadenectomy followed by postop- IIIC With positive nodes with extracapsular spread erative radiation therapy to the involved groin and pelvis. Tumor invades other regional (2/3 upper urethra, 2/3 However, if the sentinel lymph nodes identified by mapping Stage IV upper vagina) or distant structures are histologically negative after review by an experienced Tumor invades any of the following: multidisciplinary team, no further treatment is indicated. (i) Upper urethra and/or vaginal mucosa, bladder It should be emphasized that optimal candidates for sen- IVA mucosa, rectal mucosa, or fixed to pelvic bone, tinel lymph node mapping are patients who have lateral T or (ii) Fixed or ulcerated inguinofemoral lymph nodes T unifocal vulvar cancers <4 cm diameter with nonpalpable IVB Any distant metastasis including pelvic lymph nodes groin nodes [10]. This procedure is less accurate in patients The depth of invasion is defined as the measurement of the tumor from the with midline vulvar lesions or those with advanced stage epithelial-stromal junction of the adjacent most superficial dermal papilla to disease and clinically palpable inguinal nodes [17]. the deepest point of invasion. 5. Superficial Inguinal Lymphadenectomy Many surgeons concerned about the accuracy of sentinel lymph mapping have elected to perform superficial inguinal lymphadenectomy as the treatment of choice in patients with early stage vulvar cancer, believing that the superficial inguinal nodes are themselves “sentinel nodes.” Specifically, all inguinal lymph nodes above the cribriform fascia are removed en bloc (Figure 4). Approximately 8–10 lymph nodes are excised, and the saphenous vein is preserved in order to decrease the frequency of postoperative lower extremity lymphedema [18, 19]. Berman and coworkers [20] reported the outcomes of 50 patients with T vulvar cancers <1 cm diameter with stromal invasion >5mm who underwent radical wide excision and superficial inguinal lymphadenectomy. Women with positive superficial inguinal nodes underwent deep inguinal lymphadenectomy and radiation, whereas patients with negative superficial inguinal Figure 3: Sentinel lymph node mapping. Sentinel lymph nodes nodes received no further treatment. There were no isolated are localized by perilesional injection of 99 mTc radiocolloid and groin recurrences noted during a follow-up period of 36 isosulfan blue dye. months. Importantly, only 1 patient died of recurrent cancer, and wound complications were observed in only 12% of patients. These authors concluded that radical wide [10] performed the sentinel node procedure in 623 groins of excision of the primary lesion and superficial inguinal 403 assessable patients. Two hundred fifty-nine patients with lymphadenectomy was the treatment of choice for most unifocal vulvar cancers <4 cm diameter and negative sentinel women with early stage vulvar cancer and no evidence of nodes were followed without additional therapy for a median enlarged inguinal lymph nodes on clinical examination. A of 35 months. Six groin recurrences (2.3%) were observed, persisting concern of this approach has been a significant and the 3-year survival of these patients was 97%. Impor- but low incidence of groin recurrence in patients with tantly, both short-term morbidity and long-term morbidity negative superficial inguinal lymph nodes at the time of 4 International Journal of Surgical Oncology Figure 5: Radical wide excision and bilateral inguinofemoral Figure 4: Radical wide excision and ipsilateral superficial inguinal lymphadenectomy is performed for midline vulvar cancers. This lymphadenectomy is performed for lateral T or T vulvar cancers. 1 2 illustration depicts the right superficial inguinal lymph nodes and All lymph nodes above the cribriform fascia are removed and the the left deep femoral lymph nodes which are seen along the medial saphenous vein is preserved. aspect of the fossa ovalis. lymphadenectomy. Two investigators have reported a 4– At one time, patients with positive superficial or deep 7% incidence of subsequent ipsilateral groin failure after inguinal nodes were treated by pelvic lymphadenectomy. negative primary superficial groin dissection [21, 22]. This However, a prospective trial conducted by the Gynecologic is worrisome since the majority of patients with groin Oncology Group showed that patients with inguinal lymph recurrence died of their disease. However, these studies were node metastasis at the time of groin dissection who were retrospective and in one series [21] the anatomic location treated by postoperative inguinal and pelvic radiation had of the primary vulvar lesion was not reported. In the most a significant survival advantage when compared to similar recent investigation [22], vulvar cancers that recurred in the patients treated by pelvic lymphadenectomy [25]. Patients in groin after negative superficial inguinal lymphadenectomy the radiation therapy arm received 45–50 Gy to the involved were central periclitoral lesions and the number of lymph groin and pelvis, whereas patients randomized to pelvic nodes removed was small (∼3 per groin). Therefore, these lymphadenectomy underwent a standard extraperitoneal authors recommend superficial inguinal lymphadenectomy excision of the obturator, external iliac, internal iliac, and as the initial surgical approach in patients with lateral Stage I common iliac lymph nodes. This trial showed a statistically or Stage II vulvar cancers provided that an adequate number significant survival advantage to patients in the radiation of superficial inguinal lymph nodes (8–10) are removed [22]. therapy arm (68% versus 54% observed survival) on interim Currently, superficial inguinal lymphadenectomy should be analysis [26]. Therefore, most vulvar cancer patients with considered only in patients with lateral T and T vulvar 1 2 positive superficial or deep inguinal lymph node metas- cancers having >1 mm stromal invasion and no clinical tases at the time of inguinal lymphadenectomy are treated evidence of enlarged groin nodes. now by postoperative radiation to the involved groin and pelvis. 6. Deep Inguinal Lymphadenectomy Anatomic studies have indicated that some superficial 7. Unilateral versus Bilateral inguinal nodes may be located within the interstices of the Inguinal Lymphadenectomy cribriform fascia and could be missed by purely superficial inguinal lymphadenectomy [23]. Therefore, some surgeons Anatomic studies have confirmed that efferent lymphatics choose to perform deep inguinal lymphadenectomy rou- from the lateral vulva drain initially to the ipsilateral tinely at the time of superficial inguinal lymphadenectomy. superficial inguinal lymph nodes [2, 27]. Likewise, lateral The deep femoral lymph nodes are always located within vulvar cancers (>1 cm beyond the midline) do not spread the opening of the fossa ovalis medial to the femoral vein, to the contralateral inguinal lymph nodes without first and no lymph nodes are distal to the lower margin of the involving the ipsilateral inguinal nodes [27, 28]. These fossa ovalis or lateral to the femoral vein (Figure 5). For this anatomic observations have led toclinicaltrials evaluating reason, incision of the deep fascia of the adductor canal and the efficacy of radical wide excision and ipsilateral inguinal dissection of the femoral vessels, sometimes performed as lymphadenectomy in the treatment of lateral vulvar cancers. part of this procedure, are unnecessary. This is important DeSimone and coworkers [29], for example, treated 122 since deep fascial incision and stripping of the femoral patients with lateral T or T vulvar cancers by radical 1 2 vessels is associated with postoperative wound breakdown, vulvectomy (N = 60) or radical wide excision (N = 62) lymphocyst formation, and lower extremity edema in up to and bilateral inguinal lymphadenectomy. Twenty-six patients 40% of cases [11, 24]. (21%) had ipsilateral inguinal lymph node metastases, but International Journal of Surgical Oncology 5 there were no cases of spread to the contralateral inguinal [2] A.A.Plentl and E. A. Friedman, Lymphatic System of the Female Genitalia: The Morphologic Basis of Oncologic Diagnosis lymph nodes. Patients with positive inguinal nodes were and Therapy, Saunders, Philadelphia, Pa, USA, 1971. treated by postoperative radiation therapy to the involved [3] D. C.Figge, H.K.Tamimi, and B.E.Greer, “Lymphaticspread groin and pelvis. All patients in the study were followed in carcinoma of the vulva,” American Journal of Obstetrics and periodically by clinical examinations 10–195 months (mean Gynecology, vol. 152, no. 4, pp. 387–394, 1985. 59 months) after treatment. Eighteen patients (15%) devel- [4] S.Way,“Carcinoma ofthe vulva,” American Journal of oped recurrent vulvar cancer—13 to the ipsilateral vulvar Obstetrics and Gynecology, vol. 79, pp. 692–697, 1960. skin, 2 to the ipsilateral groin, and 3 to the lung. There [5] N. F.Hacker, R. S. Leuchter, J.S.Berek, T. W.Castaldo, and L. were no recurrences to the contralateral vulvar skin or groin. D. Lagasse, “Radical vulvectomy and bilateral inguinal lym- Likewise, there was no difference in the local recurrence rate phadenectomy through separate groin incisions,” Obstetrics of patients treated by radical vulvectomy versus those treated and Gynecology, vol. 58, no. 5, pp. 574–579, 1981. by radical wide excision. The 5-year disease-free survival was [6] J.M.Heaps,Y. S.Fu, F. J. Montz, N. F. Hacker,and J. S. Berek, 98% for patients with T lesions and 93% for patients with T “Surgical-pathologic variables predictive of local recurrence in 1 2 squamous cell carcinoma of the vulva,” Gynecologic Oncology, lesions. These authors concluded that women with lateral T vol. 38, no. 3, pp. 309–314, 1990. and T vulvar cancers could be treated effectively by radical [7] J. A. De Hullu, H. Hollema, S. Lolkema et al., “Vulvar wide excision and ipsilateral inguinal lymphadenectomy. carcinoma: the price of less radical surgery,” Cancer, vol. 95, There is still some controversy concerning the per- no. 11, pp. 2331–2338, 2002. formance of routine contralateral inguinofemoral lym- [8] J.A.De Hullu, H.Hollema, D. A.Piers et al., “Sentinel lymph phadenectomy in patients with lateral vulvar cancers and node procedure is highly accurate squamous cell carcinoma positive ipsilateral inguinal nodes. Isolated reports have of the vulva,” Journal of Clinical Oncology, vol. 18, no. 15, pp. indicated that contralateral inguinal lymph node metastases 2811–2816, 2000. can occur in these patients. However, the frequency of [9] R. G. Moore, K. Robison, A. K. Brown et al., “Isolated sentinel contralateral spread in these patients is extremely low, and lymph node dissection with conservative management in the risk of contralateral inguinal lymphadenectomy may patients with squamous cell carcinoma of the vulva: a outweigh its benefits, particularly if only a small number of prospective trial,” Gynecologic Oncology, vol. 109, no. 1, pp. 65–70, 2008. ipsilateral nodes are positive. [10] A. G. J. Van Der Zee, M. H. Oonk, J. A. De Hullu et al., All vulvar cancers located within 1 cm of midline struc- “Sentinel node dissection is safe in the treatment of early-stage tures (clitoris, vagina, or anus) have the potential to spread vulvar cancer,” Journal of Clinical Oncology,vol. 26, no.6, pp. to both groins, and should be treated by radical wide excision 884–889, 2008. and bilateral inguinofemoral lymphadenectomy. [11] K. N. Gaarenstroom, G. G. Kenter, J. B. Trimbos et al., “Post- operative complications after vulvectomy and inguinofemoral lymphadenectomy using separate groin incisions,” Interna- 8. Summary tional Journal of Gynecological Cancer, vol. 13, no. 4, pp. 522– The Bassett-Way operation, which emphasized en bloc 527, 2003. resection of the vulva and both groins, has been replaced [12] T. Kim, A. E. Giuliano, and G. H. Lyman, “Lymphatic mapping and sentinel lymph node biopsy in early-stage breast by radical wide excision and selective inguinal lymphadenec- carcinoma: a metaanalysis,” Cancer, vol. 106, no. 1, pp. 4–16, tomy through separate groin incisions. The specific type of inguinal lymphadenectomy indicated depends on the stage [13] R. E. Mansel, L. Fallowfield, M. Kissin et al., “Randomized and location of each cancer. Early stage lateral vulvar cancers multicenter trial of sentinel node biopsy versus standard can be treated safely by radical wide excision and ipsilat- axillary treatment in operable breast cancer: the ALMANAC eral superficial inguinal lymphadenectomy, whereas central trial,” Journal of the National Cancer Institute, vol. 98, no. 9, vulvar cancers require bilateral inguinal lymphadenectomy. pp. 599–609, 2006. Deep inguinal lymphadenectomy, which involves surgical [14] T. J. Selman, D. M.Luesley, N. Acheson,K. S.Khan, and C. H. removal of the deep femoral nodes, is indicated in patients Mann, “A systematic review of the accuracy of diagnostic tests with centrally located early stage vulvar cancers, advanced for inguinal lymph node status in vulvar cancer,” Gynecologic Oncology, vol. 99, no. 1, pp. 206–214, 2005. stage vulvar cancers, and in patients with positive superficial [15] C. Louis-Sylvestre, E. Evangelista, F. Leonard, E. Itti, M. inguinal lymph nodes. The deep femoral lymph nodes Meignan, and B. J. Paniel, “Sentinel node localization should are always located medial to the femoral vein and can be interpreted with caution in midline vulvar cancer,” Gyneco- be removed without incising the deep fascia or dissecting logic Oncology, vol. 97, no. 1, pp. 151–154, 2005. the femoral vessels. Sentinel lymph node mapping should [16] C. F. Levenback, “How safe is sentinel lymph node biopsy in be offered to select patients with early stage lateral vulvar patients with vulvar cancer?” Journal of Clinical Oncology,vol. cancers as a means to avoid the postoperative morbidity 26, no. 6, pp. 828–829, 2008. associated with full inguinofemoral lymphadenectomy. [17] M. Frumovitz, P. T. Ramirez, G. Tortolero-Luna et al., “Characteristics of recurrence in patients who underwent lymphatic mapping for vulvar cancer,” Gynecologic Oncology, References vol. 92, no. 1, pp. 205–210, 2004. [1] A.Jemal, R. Siegel, E. Ward,Y.Hao, J. Xu, and M.J. Thun, [18] S. C. Plaxe, P. S. Braly, and P. R. Dottino, “A simplified approach to superficial inguinal dissection with sparing of “Cancer statistics, 2009,” CA: Cancer Journal for Clinicians,vol. 59, no. 4, pp. 225–249, 2009. the saphenous vein in patients with carcinoma of the vulva,” 6 International Journal of Surgical Oncology Surgery Gynecology and Obstetrics, vol. 176, no. 3, pp. 295–296, [19] S. H. Zhang, A. K. Sood, J. I. Sorosky, B. Anderson, and R. E. Buller, “Preservation of the saphenous vein during inguinal lymphadenectomy decreases morbidity in patients with carcinoma of the vulva,” Cancer, vol. 89, no. 7, pp. 1520– 1525, 2000. [20] M. L. Berman,J.T. Soper, W.T. Creasman, G. T. Olt, and P. J. SiSaia, “Conservative surgical management of superficially invasive stage I vulvar carcinoma,” Gynecologic Oncology,vol. 35, no. 3, pp. 352–357, 1989. [21] M. E. Gordinier, A. Malpica, T. W. Burke et al., “Groin recurrence in patients with vulvar cancer with negative nodes on superficial inguinal lymphadenectomy,” Gynecologic Oncology, vol. 90, no. 3, pp. 625–628, 2003. [22] T. O. Kirby, R. P. Rocconi,T. M.Numnum et al.,“Outcomes of stage I/II vulvar cancer patients after negative superficial inguinal lymphadenectomy,” Gynecologic Oncology,vol.98, no. 2, pp. 309–312, 2005. [23] C. N. Hudson,H. Shulver,and D. C. Lowe, “The surgery of ’inguino-femoral’ lymph nodes: is it adequate or excessive?” International Journal of Gynecological Cancer,vol.14, no.5,pp. 841–845, 2004. [24] N. Gould, S. Kamelle, T. Tillmanns et al., “Predictors of complications after inguinal lymphadenectomy,” Gynecologic Oncology, vol. 82, no. 2, pp. 329–332, 2001. [25] F. B. Stehman, B. N. Bundy, G. Thomas et al., “Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study,” International Journal of Radiation Oncology Biology Physics, vol. 24, no. 2, pp. 389–396, [26] C. Kunos, F. Simpkins, H. Gibbons, C. Tian, and H. Homesley, “Radiation therapy compared with pelvic node resection for node-positive vulvar cancer: a randomized controlled trial,” Obstetrics and Gynecology, vol. 114, no. 3, pp. 537–546, 2009. [27] H. D. Homesley, B. N. Bundy, A. Sedlis et al., “Assess- ment of current International Federation of Gynecology and Obstetrics staging of vulvar carcinoma relative to prognostic factors for survival (A Gynecologic Oncology Group Study),” American Journal of Obstetrics and Gynecology, vol. 164, no. 4, pp. 997–1004, 1991. [28] S. J. Andrews, B. T. Williams, P. D. DePriest et al., “Therapeutic implications of lymph nodal spread in lateral T and T 1 2 squamous cell carcinoma of the vulva,” Gynecologic Oncology, vol. 55, no. 1, pp. 41–46, 1994. [29] C. P. DeSimone, J. S. Van Ness, A. L. Cooper et al., “The treatment of lateral T1 and T2 squamous cell carcinomas of the vulva confined to the labium majus or minus,” Gynecologic Oncology, vol. 104, no. 2, pp. 390–395, 2007. 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Selective Inguinal Lymphadenectomy in the Treatment of Invasive Squamous Cell Carcinoma of the Vulva

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Abstract

Hindawi Publishing Corporation International Journal of Surgical Oncology Volume 2011, Article ID 284374, 6 pages doi:10.1155/2011/284374 Review Article Selective Inguinal Lymphadenectomy in the Treatment of Invasive Squamous Cell Carcinoma of the Vulva Christopher P. DeSimone, Jeffrey Elder, and John R. van Nagell Jr. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center- Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA Correspondence should be addressed to Christopher P. DeSimone, cpdesi00@uky.edu Received 6 January 2011; Accepted 5 April 2011 Academic Editor: E. W. Martin Copyright © 2011 Christopher P. DeSimone et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. En bloc radical vulvectomy with bilateral inguinofemoral lymphadenectomy has now been replaced by radical wide excision and selective inguinal lymphadenectomy based on the stage and location of invasive vulvar cancer. Early stage lateral cancers can be effectively treated by radical wide excision and ipsilateral superficial inguinal lymphadenectomy. Lymph node mapping using perilesional injection of radiocolloid and blue dye may identify sentinel lymph nodes which can be removed, thereby avoiding the morbidity of full inguinal lymphadenectomy in selected patients with early stage disease. 1. Introduction the contralateral inguinal lymph nodes if there is no evidence of ipsilateral lymph node metastases. Likewise, it is unusual Although squamous cell carcinoma of the vulva is not com- for the deep inguinal nodes (below the cribriform fascia) to mon, it is occurring with increasing frequency in younger be involved in the absence of superficial inguinal lymph node women, particularly in those exposed to human papilloma spread. The current International Federation of Gynecology virus (HPV). With efforts at education, many patients are and ObstetricsStaging System forvulvarcancerisnow based presenting with early stage disease which is amenable to on surgical findings as illustrated in Table 1 and reflects the surgery. This year, there will be approximately 3500 new extent and location of inguinal lymph node metastases. casesofvulvarcancerinthe United States, representing 5% of all gynecologic cancers [1]. The surgical management of 3. Surgery of the Primary Vulvar Lesion this disease has evolved from en bloc resection of the entire vulva with bilateral superficial and deep inguinofemoral lym- The Basset-Way operation which was the standard of care phadenectomy to a more conservative approach involving in the operative management of patients with vulvar cancer radical wide excision of the primary lesion and specific included the en bloc resection of the primary lesion and types of inguinal lymphadenectomy based on the stage and surrounding vulvarskinaswell asthe skin over both groins anatomic location of disease. (Figure 2(a))[4]. Although this procedure was curative in the majority of cases, the wound defect was significant and incisional breakdown and lymphedema of both lower 2. Anatomic Pathways of Spread and Staging extremities were common. Currently, the surgical treatment The lymphatic drainage of the vulva has been studied of vulvar cancer involves radical wide excision of the primary extensively and described in numerous publications [2, 3]. lesion and inguinal lymphadenectomy through separate Generally, lateralizing lesions (>1cm beyond the midline) groin incisions (Figure 2(b))[5]. Heaps and colleagues [6] drain to the ipsilateral superficial inguinal lymph nodes, reported that local control of vulvar cancers could be whereas midline lesions can drain to either side (Figure 1). achieved in 100% of cases provided that a 1 cm margin of It is extremely rare for lateralizing vulvar cancers to spread to normal skin was included in the surgical specimen. These 2 International Journal of Surgical Oncology (a) (b) Figure 1: Lateral vulvar lesions >1 cm from the midline (a) spread initially to the ipsilateral superficial inguinal lymph nodes, whereas midline lesions can spread to both groins (b). (a) (b) Figure 2: The Bassett-Way operation includes en bloc radical resection of the primary lesion and surrounding vulvar skin as well as the skin over both groins (a). Radical wide excision of the vulvar cancer includes a margin of at least 1 cm of normal skin around the entire lesion. Inguinal lymphadenectomy is performed through separate groin incisions (b). observations were confirmed by De Hullu and coworkers [7] a method to identify regional lymph node metastases in who reported that there was no local recurrence of T or breast cancer [12, 13] and cutaneous melanoma [4]and has T vulvar cancers when a margin of at least 8 mm normal now been evaluated in patients with early stage vulvar cancer. skin was excised with the primary lesion. In contrast, patients Specifically, 1-2 mCi of radiocolloid is injected intradermally with a margin of <8 mm had a local recurrence rate of 22%. around the lesion (Figure 3), and a hand held gamma At present, it is recommended that a margin of at least 1 cm detection device is used to identify the sentinel lymph of normal skin around the circumference of the primary node(s). Recently, lymphoscintigraphy has been combined vulvar lesion be included in the surgical specimen and that with intraoperative perilesional injection of isosulfan blue the underlying subcutaneous tissue be removed to the level as a method to identify sentinel nodes in the inguinal area. of the perineal fascia. Inguinal lymphadenectomy is then Localization of the sentinel node(s) is usually apparent 5–15 performed through separate incisions. minutes after injection of blue dye and 30 minutes after injec- tion of radiocolloid. Selman and colleagues [14] performed a systematic review of the accuracy of sentinel lymph node 4. Sentinel Lymphadenectomy detection in identifying inguinal lymph node metastases in Sentinel lymph node excision is now being recommended in vulvar cancer and reported that the combination of 99 mTc selected patients with early stage squamous cell carcinoma radiocolloid and isosulfan blue dye successfully detected as a means to avoid the operative morbidity associated with sentinel lymph nodes in 97% of cases. It also had a negative inguinofemoral lymphadenectomy [8–10]. It is estimated predictive value (NPV) of 99.1%. Further analysis has that only 25–30% of patients with early stage vulvar cancer indicated that sentinel lymph node mapping is most accurate have lymph node metastases, and complete inguinofemoral in patients with early stage lateral vulvar cancers [15]. lymphadenectomy is associated with postoperative wound A persisting concern about sentinel lymph node mapping complications and lower extremity edema in 30–40% of in vulvar cancer is the frequency of groin recurrences in patients [11]. Sentinel lymph node mapping using radio- patients with negative sentinel lymph nodes. In a multi- labelled ultrafiltered sulfur colloid was initially reported as institutional observational study, Van Der Zee and coworkers International Journal of Surgical Oncology 3 Table 1: FIGO staging of invasive cancer of the vulva. of patients having sentinel node excision were significantly reduced when compared to that of women undergoing Stage I Tumor confined to the vulva complete inguinofemoral lymphadenectomy. These authors Lesions ≤2 cm in size confined to the vulva or concluded that sentinel node dissection, performed by a IA perineum and with stromal invasion ≤1.0 mm , quality-controlled multidisciplinary team, should be offered no nodal metastasis to selected patients with early stage vulvar cancer as a Lesions >2 cm in size confined to the vulva or means to avoid the postoperative morbidity associated with IB perineum with stromal invasion greater than 1.0 mm , inguinofemoral lymphadenectomy. no nodal metastasis There is a definite learning curve in the performance Tumor of any size with extension to adjacent perineal and interpretation of lymph node mapping, and it is Stage II structures (1/3 lower urethra, 1/3 lower vagina, anus), recommended that a multidisciplinary group within each no nodal metastasis institution perform sentinel node mapping in at least 10– Tumor of any size with or without extension to adjacent 20 cases before it becomes an accepted procedure [10, 16]. Stage III perineal structures (1/3 lower urethra, 1/3 lower vagina, If sentinel lymph nodes cannot be identified by mapping or anus) with positive inguinofemoral lymph nodes if there is uncertainty concerning interpretation of findings, a IIIA With 1 lymph node metastasis (≥5 mm), superficial inguinal lymphadenectomy should be performed. (i) With 2 or more lymph node metastases (≥5 mm), Patients with a positive sentinel node should undergo a IIIB (ii) 3 or more lymph node metastases (<5 mm) full inguinofemoral lymphadenectomy followed by postop- IIIC With positive nodes with extracapsular spread erative radiation therapy to the involved groin and pelvis. Tumor invades other regional (2/3 upper urethra, 2/3 However, if the sentinel lymph nodes identified by mapping Stage IV upper vagina) or distant structures are histologically negative after review by an experienced Tumor invades any of the following: multidisciplinary team, no further treatment is indicated. (i) Upper urethra and/or vaginal mucosa, bladder It should be emphasized that optimal candidates for sen- IVA mucosa, rectal mucosa, or fixed to pelvic bone, tinel lymph node mapping are patients who have lateral T or (ii) Fixed or ulcerated inguinofemoral lymph nodes T unifocal vulvar cancers <4 cm diameter with nonpalpable IVB Any distant metastasis including pelvic lymph nodes groin nodes [10]. This procedure is less accurate in patients The depth of invasion is defined as the measurement of the tumor from the with midline vulvar lesions or those with advanced stage epithelial-stromal junction of the adjacent most superficial dermal papilla to disease and clinically palpable inguinal nodes [17]. the deepest point of invasion. 5. Superficial Inguinal Lymphadenectomy Many surgeons concerned about the accuracy of sentinel lymph mapping have elected to perform superficial inguinal lymphadenectomy as the treatment of choice in patients with early stage vulvar cancer, believing that the superficial inguinal nodes are themselves “sentinel nodes.” Specifically, all inguinal lymph nodes above the cribriform fascia are removed en bloc (Figure 4). Approximately 8–10 lymph nodes are excised, and the saphenous vein is preserved in order to decrease the frequency of postoperative lower extremity lymphedema [18, 19]. Berman and coworkers [20] reported the outcomes of 50 patients with T vulvar cancers <1 cm diameter with stromal invasion >5mm who underwent radical wide excision and superficial inguinal lymphadenectomy. Women with positive superficial inguinal nodes underwent deep inguinal lymphadenectomy and radiation, whereas patients with negative superficial inguinal Figure 3: Sentinel lymph node mapping. Sentinel lymph nodes nodes received no further treatment. There were no isolated are localized by perilesional injection of 99 mTc radiocolloid and groin recurrences noted during a follow-up period of 36 isosulfan blue dye. months. Importantly, only 1 patient died of recurrent cancer, and wound complications were observed in only 12% of patients. These authors concluded that radical wide [10] performed the sentinel node procedure in 623 groins of excision of the primary lesion and superficial inguinal 403 assessable patients. Two hundred fifty-nine patients with lymphadenectomy was the treatment of choice for most unifocal vulvar cancers <4 cm diameter and negative sentinel women with early stage vulvar cancer and no evidence of nodes were followed without additional therapy for a median enlarged inguinal lymph nodes on clinical examination. A of 35 months. Six groin recurrences (2.3%) were observed, persisting concern of this approach has been a significant and the 3-year survival of these patients was 97%. Impor- but low incidence of groin recurrence in patients with tantly, both short-term morbidity and long-term morbidity negative superficial inguinal lymph nodes at the time of 4 International Journal of Surgical Oncology Figure 5: Radical wide excision and bilateral inguinofemoral Figure 4: Radical wide excision and ipsilateral superficial inguinal lymphadenectomy is performed for midline vulvar cancers. This lymphadenectomy is performed for lateral T or T vulvar cancers. 1 2 illustration depicts the right superficial inguinal lymph nodes and All lymph nodes above the cribriform fascia are removed and the the left deep femoral lymph nodes which are seen along the medial saphenous vein is preserved. aspect of the fossa ovalis. lymphadenectomy. Two investigators have reported a 4– At one time, patients with positive superficial or deep 7% incidence of subsequent ipsilateral groin failure after inguinal nodes were treated by pelvic lymphadenectomy. negative primary superficial groin dissection [21, 22]. This However, a prospective trial conducted by the Gynecologic is worrisome since the majority of patients with groin Oncology Group showed that patients with inguinal lymph recurrence died of their disease. However, these studies were node metastasis at the time of groin dissection who were retrospective and in one series [21] the anatomic location treated by postoperative inguinal and pelvic radiation had of the primary vulvar lesion was not reported. In the most a significant survival advantage when compared to similar recent investigation [22], vulvar cancers that recurred in the patients treated by pelvic lymphadenectomy [25]. Patients in groin after negative superficial inguinal lymphadenectomy the radiation therapy arm received 45–50 Gy to the involved were central periclitoral lesions and the number of lymph groin and pelvis, whereas patients randomized to pelvic nodes removed was small (∼3 per groin). Therefore, these lymphadenectomy underwent a standard extraperitoneal authors recommend superficial inguinal lymphadenectomy excision of the obturator, external iliac, internal iliac, and as the initial surgical approach in patients with lateral Stage I common iliac lymph nodes. This trial showed a statistically or Stage II vulvar cancers provided that an adequate number significant survival advantage to patients in the radiation of superficial inguinal lymph nodes (8–10) are removed [22]. therapy arm (68% versus 54% observed survival) on interim Currently, superficial inguinal lymphadenectomy should be analysis [26]. Therefore, most vulvar cancer patients with considered only in patients with lateral T and T vulvar 1 2 positive superficial or deep inguinal lymph node metas- cancers having >1 mm stromal invasion and no clinical tases at the time of inguinal lymphadenectomy are treated evidence of enlarged groin nodes. now by postoperative radiation to the involved groin and pelvis. 6. Deep Inguinal Lymphadenectomy Anatomic studies have indicated that some superficial 7. Unilateral versus Bilateral inguinal nodes may be located within the interstices of the Inguinal Lymphadenectomy cribriform fascia and could be missed by purely superficial inguinal lymphadenectomy [23]. Therefore, some surgeons Anatomic studies have confirmed that efferent lymphatics choose to perform deep inguinal lymphadenectomy rou- from the lateral vulva drain initially to the ipsilateral tinely at the time of superficial inguinal lymphadenectomy. superficial inguinal lymph nodes [2, 27]. Likewise, lateral The deep femoral lymph nodes are always located within vulvar cancers (>1 cm beyond the midline) do not spread the opening of the fossa ovalis medial to the femoral vein, to the contralateral inguinal lymph nodes without first and no lymph nodes are distal to the lower margin of the involving the ipsilateral inguinal nodes [27, 28]. These fossa ovalis or lateral to the femoral vein (Figure 5). For this anatomic observations have led toclinicaltrials evaluating reason, incision of the deep fascia of the adductor canal and the efficacy of radical wide excision and ipsilateral inguinal dissection of the femoral vessels, sometimes performed as lymphadenectomy in the treatment of lateral vulvar cancers. part of this procedure, are unnecessary. This is important DeSimone and coworkers [29], for example, treated 122 since deep fascial incision and stripping of the femoral patients with lateral T or T vulvar cancers by radical 1 2 vessels is associated with postoperative wound breakdown, vulvectomy (N = 60) or radical wide excision (N = 62) lymphocyst formation, and lower extremity edema in up to and bilateral inguinal lymphadenectomy. Twenty-six patients 40% of cases [11, 24]. (21%) had ipsilateral inguinal lymph node metastases, but International Journal of Surgical Oncology 5 there were no cases of spread to the contralateral inguinal [2] A.A.Plentl and E. A. Friedman, Lymphatic System of the Female Genitalia: The Morphologic Basis of Oncologic Diagnosis lymph nodes. Patients with positive inguinal nodes were and Therapy, Saunders, Philadelphia, Pa, USA, 1971. treated by postoperative radiation therapy to the involved [3] D. C.Figge, H.K.Tamimi, and B.E.Greer, “Lymphaticspread groin and pelvis. 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