Gynecologic Oncology 73, 72–75 (1999) Article ID gyno.1998.5271, available online at http://www.idealibrary.com on
Lateral Microscopic Extension of Squamous Cell Carcinoma of the Vulva 1 Mitchel S. Hoffman, M.D., Sivaselvi Gunesakaran, M.D.,* Hector Arango, M.D., Steven DeCesare, M.D., James V. Fiorica, M.D., Michael Parsons, M.D., and Denis Cavanagh, M.D. Department of Obstetrics and Gynecology and *Department of Pathology, The University of South Florida College of Medicine, Tampa, Florida 33606 Received June 23, 1998
than 7 mm [15]. In another study, 15 of 64 Stage I (clinical) cancers demonstrated microscopic surface noncontiguity near the primary tumor [16]. In obtaining a tumor-free margin, it would be important to have some idea of the frequency and average radial distance of occult microscopic spread of these tumors beyond what is grossly evident. The purpose of this study was to measure the radial occult microscopic spread of tumor in patients with invasive squamous cell carcinoma of the vulva.
Purpose. The aim of this study was to measure the radial occult microscopic spread of tumor in patients with invasive squamous cell carcinoma of the vulva. Materials and Methods. In the operating room the gross tumor border was marked. The pathologist took a radial section in each quadrant and measured the distance of occult lateral spread of the tumor. Results. From 7/01/93 to 6/30/96, 24 tumors from 21 patients were studied. The mean maximum tumor diameter was 3.2 cm (0.5–7.0) and the mean depth of invasion was 9.1 mm (1.1–28.0). The gross and microscopic extent correlated in 20 tumors. Maximum lateral microscopic extent of the other 4 tumors was 3.5, 5 (to the margin), 10, and 16 mm. These 4 tumors were ulcerative and infiltrative and arose from or involved mucosa. Conclusion. The gross and microscopic periphery of most invasive squamous vulvar cancers are approximately the same. Ulcerative tumors with an infiltrative pattern of invasion which involve mucosal epithelium may be more likely to extend beyond what is grossly apparent. Measurement of the tumor-free margin should be included in future studies. © 1999 Academic Press
MATERIALS AND METHODS All patients undergoing primary excision of invasive squamous cell carcinoma of the vulva were eligible. Patients who had previously undergone an excisional biopsy were excluded. Patients with Bartholin tumors, metastatic tumors, and tumors with less than 1 mm of invasion were also excluded. Immediately prior to excision the gross extent of the invasive tumor was circumferentially marked (tattooed with India ink or methylene blue or tagged with four silk sutures). Following removal the specimen was oriented and sent to the pathologist who marked the gross epithelial extent with India ink. A radial section was taken in each quadrant and the distance of occult lateral spread of the tumor was measured. Occult lateral spread was measured from the grossly assessed peripheral extent of the tumor on the surface to the lateral-most aspect of the invasive tumor in the subepithelial connective tissue (Fig. 1). In the event of a positive margin, the distance to the margin was recorded as such. Lateral microscopic extension beyond the grossly apparent tumor border was considered to be insignificant if it measured less than 1 mm. As most lesions were exophytic, the depth of invasion measurement was calculated by subtracting the thickness of epithelium over adjacent dermal papilla from the total thickness of the tumor. Total thickness of the tumor was measured from the surface to the deepest point of invasion [3]. The growth pattern of the tumors was categorized into two groups: (a) pushing when there are broad smooth fronds of invasion and (b) infiltrative (Syn: diffuse, stellate, or spray pattern) when the invasive
INTRODUCTION The standard treatment for invasive squamous cell carcinoma of the vulva has been radical vulvectomy with bilateral inguinal lymphadenectomy. During the past decade several modifications of this treatment have been put into practice [1]. For selected cases of early or well-regionalized tumors, several studies have reported good results with a “modified” radical vulvectomy [2–11]. Depending on the radicality of the excision, the anatomy of the vulva is such that compromise to local organs, sexual function, and appearance is frequent [2, 12–14]. The issue of “margins” is therefore important. Several authors have stated that a 2- to 3-cm normal tissue margin should be obtained [2–5]. There is no clear basis for this, however. The results of one study did suggest that local recurrence was decreased when the resected tumor-free margin was greater 1
Presented at the 47th Annual Meeting of The Society of Pelvic Surgeons, November 15, 1997. 0090-8258/99 $30.00 Copyright © 1999 by Academic Press All rights of reproduction in any form reserved.
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FIG. 1. (Top) Diagram of longitudinal cross-section demonstrating occult microscopic extension of tumor (in black) beyond the clinically apparent border. (Bottom) Diagram looking down at the tumor. The clinically apparent extent is represented by the dark line and occult microscopic extension is represented by the shaded areas. Sections in four quadrants with measurement of microscopic extension are shown.
component displays irregular cords, angulated nests, and dissociated cells, often accompanied by desmoplasia.
vasion only (2) or vulvar intraepithelial neoplasia III only (1). This left 21 patients with 24 tumors (3 patients had two separate foci which were studied separately) in the study group. The mean age of the 21 patients was 60 years (36 to 93). Local treatment consisted of modified radical vulvectomy for 16, radical vulvectomy for 4, and abdominoperineal resection in 1. Of the 24 tumors, the gross appearance was considered to be exophytic in 12, ulcerative in 8, a combination in 3, and flat in 1. The pattern of invasion was infiltrative in 12 tumors, pushing in 9, a combination in 2, and what would be best characterized as carcinoma in situ with early stromal invasion in 1. The location of the tumor was posterior vulva in 12, predominantly on one side in 7, and anterior vulva in 5. The mean maximum tumor diameter was 3.2 cm (0.5 to 7.0) and the mean depth of invasion was 9.1 mm (1.1 to 28). The gross and microscopic extent correlated in 20 tumors. This included 1 patient with a single (medial) grossly positive margin. Maximum lateral microscopic extension of the other 4 tumors was 3.5, 5 (to the margin), 10, and 16 mm. These 4 tumors were ulcerative. Three of the 4 tumors had an infiltrative pattern of invasion and 1 had a combined pattern. One of these tumors had microscopic extension from all four quadrants ranging from 6.5 to 10 mm. Two other patients had microscopic extension in two quadrants and 1 patient had microscopic extension (3.5 mm) in only one quadrant. The distance from the microscopic tumor border to the surgical margin was not evaluated in this study. The patient with microscopic extension in all four quadrants had a 4.9-cm diameter tumor (clitoris and anterior vestibule) invading to a depth of 22 mm with the tumor reported to be close to the deep surgical margin. This patient also had bilateral inguinal lymph node metastases and was treated postoperatively with radiotherapy to the vulva, whole pelvis, and groins. She has remained without evidence of recurrence 31 months following surgery. One of the 2 patients with lateral extension in two quadrants had an anterior vestibular tumor with extension 16
TABLE 1 Tabulation of Pathologic Variables According to Extension or No Extension of Tumor
RESULTS From 7/01/93 to 6/30/96, 39 patients with a primary diagnosis of invasive squamous cell carcinoma of the vulva were seen by the University of South Florida, Division of Gynecologic Oncology. Nine of these were missed by the study. Four patients had undergone excision for vulvar intraepithelial neoplasia (VIN) and were found to have invasive cancer in the specimen. Three patients with locally advanced disease were treated initially with chemo/radiotherapy. Three initially studied tumors (one from a patient with two separate vulvar tumors) were excluded after further review determined microin-
Mean age Ulcerative Infiltrative Mucosal Coexistent VIN Diameter (cm) Depth (mm) LVSI Grade 3 Nodes (1) Local recurrence
Extension
Correlation
P
81 4 4 4 0 3.57 10.7 0 0 2/4 0/4
57 4 10 2 4 3.15 8.9 1 1 5/17 5/17
0.029 0.007 NS 0.001 NS NS NS NS NS NS
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FIG. 2. Well-circumscribed, ulcerative, malignant, vulvar tumor involving mucosal epithelium.
mm beyond the gross margin at 6 o’clock and this was close to the surgical margin (urethra). In addition, she had one of eight lymph nodes positive on the left side. This patient had been treated previously with radiotherapy for carcinoma of the cervix and it was felt by the radiotherapist that additional therapeutic radiation should not be delivered. She has remained without evidence of recurrence for 44 months. The other patient with lateral extension in two quadrants was 1 of the patients with 2 tumors. She had extension beyond the gross tumor at 3 o’clock all the way to the surgical margin (vagina) which was 5 mm from the tumor. Additional resection was done at that time. She had negative lymph nodes and remains without evidence of recurrence at 16 months. The fourth patient had extension 3.5 mm beyond the tumor (clitoris and periclitoral) in one quadrant and negative lymph nodes and remains without evidence of recurrence at 12 months. Of the three patients that had two tumors each, one had lateral microscopic extension in two quadrants in one of the tumors and no extension in the other tumor and the remaining two patients had no microscopic extension from either tumor. A tabulation of pathologic variables is given in Table 1. Statistical analysis (Fisher’s exact test) must be viewed with
caution due to the small numbers. As previously stated, all 4 of the vulvar cancers with microscopic extension had ulcerative (4 of 8) tumors with an infiltrative (1 combined) growth pattern (4 of 14) and involved mucosal epithelium (4 of 6, Fig. 2). None of the 15 exophytic tumors (3 with a combination) or the 10 tumors with a noninfiltrative growth pattern had microscopic extension. Only 1 (correlation group) of the 24 tumors had lymph– vascular space involvement. A regional lymphadenectomy was done in all patients. With inclusion of the patient with 1 of 2 tumors having lateral microscopic extension in the extension group, 2 of the 4 patients had positive lymph nodes. Five of the 17 without lateral extension had positive lymph nodes (2 bilateral). Twelve of the 17 patients without microscopic extension remained without evidence of recurrent cancer at a mean follow-up of 19 months (8 to 40 months). One developed carcinoma in situ locally at 7 months, but remains free of invasive recurrence at 24 months. The remaining 4 patients without extension developed local recurrence (1 also regional) at a mean of 8.4 months (4.5 to 18 months) with 3 dead of disease at 11, 16, and 21 months. One of the 4 patients with
MICROSCOPIC EXTENSION OF VULVAR CANCER
lateral extension received postoperative radiotherapy as previously described. All 4 remain without evidence of recurrence at 12, 16, 31, and 44 months. A multivariate analysis was attempted in order to evaluate possible factors (age, tumor location, depth, diameter, growth pattern, node positivity, etc.) that might predict lateral microscopic extension of the tumor. The analysis was not possible due to the small numbers. DISCUSSION This study should be viewed as a preliminary report on the measurement of radial occult microscopic spread of tumor in patients with invasive squamous cell carcinoma of the vulva. The study does present a technique for the measurement of such spread and confirms the fact that it does occur in some patients. A preliminary conclusion is that the gross and microscopic extent of tumor correlate in the majority (83% in this study) of patients. Another preliminary conclusion is that ulcerative, infiltrative tumors that arise from or involve mucosal epithelium, especially in elderly women, may be more likely to have radial microscopic extension. A major weakness in the methodology of this study was not including radial measurements from the tumor margin to the surgical margin. This was due to omission of this important factor during the design of the study and it was not possible to retrieve this information from the already-processed specimens. Identifying a subgroup of patients with radial microscopic extension of tumor would only be of importance if the tumor-free surgical margin had similar importance to that described by Heaps et al. [15]. Therefore, a future study on the radial occult microscopic extension of these tumors should have a large number of patients which are actually found to have microscopic extension and the tumor-free margin should be included in the analysis. REFERENCES 1. Hoffman MS, Roberts WA, LaPolla JP, Cavanagh D: Recent modifications in the treatment of invasive squamous cell carcinoma of the vulva. Obstet Gynecol Surv 44:227–233, 1989
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2. DiSaia PT, Creasman WT, Rich WM: An alternative approach to early cancer of the vulva. Am J Obstet Gynecol 133:825– 832, 1979 3. Hacker NF, Berek JS, Lagasse LD, Nieberg RK, Leuchter RS: Individualization of treatment for Stage I squamous cell vulvar carcinoma. Obstet Gynecol 63:155–162, 1984 4. Burrell MD, Franklin WE, Campion MJ, Crozier MA, Stacy DW: The modified radical vulvectomy with groin dissection: an eight-year experience. Am J Obstet Gynecol 159:715–722, 1988 5. Berman MI, Soper JT, Creasman WT, Olt GT, DiSaia PJ: Conservative surgical management of superficially invasive Stage I vulvar carcinoma. Gynecol Oncol 35:352–357, 1989 6. Sutton GP, Miser MR, Stehman FB, Look KY, Ehrlich CE: Trends in the operative management of invasive squamous cell carcinoma of the vulva at Indiana University, 1974 –1988. Am J Obstet Gynecol 164:1472–1481, 1991 7. 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. Obstet Gynecol 79:490 – 497, 1992 8. Hoffman MS, Roberts WS, Finan MA, Fiorica JV, Bryson SPC, Rulfolo EH, Cavanagh D: A comparative study of radical vulvectomy and modified radical vulvectomy for the treatment of invasive squamous cell carcinoma of the vulva. Gynecol Oncol 45:192–197, 1992 9. Lin JY, DuBeshter B, Angel C, Dvoretsky PM: Morbidity and recurrence with modifications of radical vulvectomy and groin dissection. Gynecol Oncol 47:80 – 86, 1992 10. Farias-Eisner R, Cirisano FD, Grouse D, Leuchter RS, Karlan BY, Lagasse LD, Berek JS: Conservative and individualized surgery for early squamous carcinoma of the vulva: the treatment of choice for Stage I and II (T 1–2 N 0 –1 M 0) disease. Gynecol Oncol 53:55–58, 1994 11. Burke TW, Levenback C, Coleman RL, Morris M, Silva EG, Gershenson DM: Surgical therapy of T1 and T2 vulvar carcinoma; further experience with radical wide excision and selective inguinal lymphadenectomy. Gynecol Oncol 57:215–220, 1995 12. Andersen BL, Jacker NF: Psychosexual adjustment after vulvar surgery. Obstet Gynecol 62:457– 462, 1983 13. Hoffman MS, Roberts WS, LaPolla JP, Fiorica JV, Cavanagh D: Carcinoma of the vulva involving the perianal or anal skin. Gynecol Oncol 35:215–218, 1989 14. Reid G, Delancey J, Hopkins M, Roberts J, Morley G: Urinary incontinence following radical vulvectomy. Obstet Gynecol 75:852– 858, 1990 15. Heaps JM, Fu YS, Montz FJ, Hacker NF, Berek JS: Surgical–pathologic variables predictive of local recurrence in squamous carcinoma of the vulva. Gynecol Oncol 38:309 –314, 1990 16. Ross MJ, Ehrmann RL: Histologic prognosticators in Stage 1 squamous cell carcinoma of the vulva. Obstet Gynecol 70:774 –784, 1987