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Verrucous carcinoma of the female genital tract: Report of a case and review of the literature
GYNECOLOGIC
ONCOLOGY
30, 427-434 (1988)
CASE REPORT Verrucous Carcinoma of the Female Genital Tract: Report of a Case and Review of the Literature ERIK SOGAARD ANDERSEN, *Departments
of Obstetrics
M.D.,*
AND
INGE MARIE SORENSEN,
and Gynecology and 7Department of Pathology, Section North, 8800 Viborg, Denmark
M.D.?
Aalborg
Hospital,
Received February 11, 1987 Verrucous carcinoma (VC) of the female genital tract is a rare lesion, primarily affecting postmenopausal women. A case of VC of the vulva is reported, bringing the total number of VC of the female genital tract to 89. VC is a slowly growing, locally “pushing” tumor with a rather benign histologic appearance, and the clinical and histologic characteristics are described on the basis of the present report and a review of the literature. The treatment of VC is still a matter of discussion. It seems logical to treat the tumor by wide local excision, taking the lack of proof of spontaneous metastasis into consideration. Radiation therapy should be contraindicated, and local application of podophyllin, bleomycin therapy, and cryosurgery are ineffective methods in the treatment of VC. o 1988 Academic press. IN.
INTRODUCTION
Ackerman [l], in 1948, described the clinical and histopathologic features of a distinct variant of epidermoid carcinoma of the oral cavity and designated the tumor verrucous carcinoma (VC). The female genital tract as a possible site of this tumor was suggested by Goethals et al. [2], and in 1966 Kraus and PerezMesa [3] reported the first two cases of VC of the female genital tract, one in the vagina and one in the vulva. According to the number of cases of VC of the female genital tract reported since 1966, it is a rare lesion. There still exist diagnostic difficulties and treatment is a matter of debate. The present paper presents a case of VC of the female genital tract, located in the vulva, and the literature is reviewed. The clinical and histologic features are described and the therapeutic aspects are discussed on the basis of the literature. CASE REPORT
An U-year-old woman, without previous gynecological disease, was admitted to a local hospital, April 29, 1985. She had complained of severe genital itching for 6 months. Examination revealed a 5 x 4 x 3.5 cm cauliflower-like tumor, 427 0090-8258/88 $1.50 Copyright Q 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.
428
ANDERSEN
AND
SORENSEN
originating in the left labium majus and involving the clitoral region. The tumor was excised. Microscopically, the diagnosis of a hyperkeratotic papilloma was made, but the possibility that the tumor was a verrucous carcinoma was considered. Six months later, January 7, 1986, the patient had a follow-up visit. The genital itching was still present. Physical examination showed a marked lichenization of the skin of the vulva region. Biopsies were taken, the microscopic examination showing severe keratinizing squamous dysplasia. The patient was then admitted to us. The biopsies were repeated, showing the same alterations of the epithelium; the previous specimens were reviewed and new deeper slides were cut from the original paraffin blocks. Microscopic jindings. The surface of the tumor was covered with papillary fronds composed of highly differentiated hyperkeratotic, parakeratotic, and acanthotic stratified squamous epithelium without major cellular polymorphism (Fig. 1). A few dyskeratotic cells and a few keratin pearls were seen in the deeper layer of the epithelium. A few islands of infiltrating squamous epithelium with nuclear atypia and keratinization were seen in the underlying inflammated stroma (Fig. 2). There was an abrupt transition between the lesion and the normal epithelium. In an adjacent area a focus of severe keratinizing squamous dysplasia was found (Fig. 3). Immunohistochemical investigation (rapid anti-bovine papilloma virus Type IBPVI-Dacopat California, #3580 lot #014 was used) revealed no human papilloma virus inclusions in the epithelium of the VC nor in the later biopsies. By electron microscopy the VC showed ultrastructural features similar to those of normal stratified squamous epithelium with easily identifiable tonofibrils and desmosomes. A simple vulvectomy was made, after repeated biopsies had shown a persisting severe keratinizing dysplasia. Microscopic examination of the vulvectomy preparation confirmed these alterations. Furthermore, minor areas of atrophic as well as hypertrophic dystrophic epithelial lesions were seen. There was no sign of persistence of recurrence of the VC. At the present time, 21 months after primary treatment, the patient is alive without any evidence of disease. DISCUSSION Verrucous carcinoma of the female genital tract is a rare lesion. A review of the literature revealed 88 cases previously reported [3-251. The location of the tumor and age characteristics are shown in Table 1. It is primarily a tumor of the postmenopausal age and involvement of the vulva and the cervix seems more common than involvement of the vagina. The patients with involvement of the uterine cervix seem to be slightly younger than patients with the tumor located in the vagina and the vulva. The etiology of VC of the female genital tract is unknown. In cases of verrucous carcinoma of the oral cavity and larynx, poor dental hygiene, tobacco chewing, and pipe smoking have been associated with the tumor [1,3,4,7]. Poor penile hygiene has been linked to the cases of VC of the penis [5,7] and poor perineal hygiene has been pointed out as a possible predisposing factor in cases of VC of the vulva [22]. Much evidence is accumulating indicating human papilloma
CASE
REPORTS
429
FIG. 1. Verrucous carcinoma. Papillary fronds of highly differentiated, hyperkeratotic, parakeratotic and acanthotic epithelium. (Hematoxylin - eosin, x 17.)
virus (HPV) as either the causative agent or a likely cofactor in the development of VC, since HPV has been found associated with this tumor [8,26-291. Further investigation is needed to make any final conclusions about the etiology of VC of the female genital tract. We were not able to demonstrate HPV inclusions. Macroscopically, VC is generally described as a cauliflower-like tumor [ 1,361. The color is greyish-white to red and the surface often shows signs of infection and ulceration. The size of the tumor may vary from less than 1 cm to more than 10 cm in diameter. The tumor is well-demarcated, growing slowly and pushing the surrounding tissue aside rather than infiltrating. As described by Kraus and Perez-Mesa [3]: “A slow but relentlessly expanding tumor.” Inflammatory enlargement of the regional lymph nodes is often present [5], and the tumor often grows around the lymph nodes rather than metastasizing to them
UA61.
430
ANDERSEN AND SORENSEN
FIG. 2. Verrucous carcinoma. A focus of invasion (arrow) in the underlying stroma. (Hematoxylin - eosin, X75.)
The frequency of metastasis to regional lymph nodes in cases of VC of the female genital tract is very low. Lymph node metastasis has been described in 5 cases [5,7,10,24,25], and in all cases the patients had been treated by primary radiation. No cases of spontaneous metastasis of VC of the female genital tract to regional lymph nodes have been reported. In two cases, histologically confirmed pulmonary metastasis of VC of the female genital tract has been reported [23,251. The tumor seems to be more aggressive in recurrent lesions [ 12,251.However, in most of these cases, the primary treatment had been radiation. There is generally agreement of the microscopic appearance of VC [1,4,6,30351. VC is a papillomatous tumor with a well-differentiated stratified squamous epithelium. The outer layers show pronounced hyperkeratosis and parakeratosis and in the deeper parts of the epithelium acanthosis is a main feature. There is only minimal polymorphism and mitotic figures are rare. Koilocytosis is a common finding. The lack of central connective tissue support is an important characteristic differentiating this tumor from benign condyloma. In VC fibrovascular cores are limited to the superficial parts of the tumor, unlike the condyloma in which the fibrovascular core extends from the deepest parts to the surface. This explains why superficially taken biopsies are of limited value in the cases of VC. To ensure a precise diagnosis, the whole tumor should be excised and presented to the pathologist. The basement membrane is usually intact, but occasionally, as in the present case, groups of invasive tumor cells are seen [23,35]. The stroma is characterized by a pronounced inflammatory response, the stroma containing
CASE
431
REPORTS
FIG. 3. Extended areas of severe keratinizing squamous dysplasia adjacent to the verrucous carcinoma. (Hematoxylin - eosin, x 96.)
lymphocytes, plasma cells, scattered eosiniphils, and occasionally micro-abscesses are formed. In a few cases, four patients in three reports [4,6,22], intraepithelial neoplasia has been described in areas adjacent to the tumor. In the present case, a severe keratinizing, squamous dysplasia was found in relation to the verrucous carcinoma and in the vulvectomy specimen. Electron microscopic studies show an appearance similar to that of normal stratified squamous epithelium [6,35]. Tonofibrils and desmosomes are easily identifiable. The treatment of verrucous carcinoma of the female genital tract is still a matter of discussion. The mode of treatment and the results obtained in previously reported cases are shown in Table 2. Despite the benign histologic appearance of VC, and the very low rate of TABLE 1 THE LOCATION
Location Vulva Cervix Vagina Total
OF VERRUCOUS CARCINOMAS OF THE FEMALE CHARACTERISTICS
GENITAL
TRACT AND THE AGE
Number
Mean age
>40 years (%)
48 30 10 88
58.3 51.0 56.4 55.6
39 (83) 21 (70) 9 (90) 69 (78)
432
ANDERSEN
AND
SORENSEN
TABLE 2 THE RESULTS OF TREATMENT OF VERRUCOUSCARCINOMA OF THE FEMALE GENITAL TRACT (PREVIOUSLY PUBLISHED CASES)
Vulva NED DOD AWD Cervix NED DOD AWD Vagina NED DOD AWD
No.
Surgery
Radiation
48’ 31 14 3 30 17 7” 3 10 8 2 0
34 28 5 1 14 12 2
1
7 6 I
Combination
1 11” 3 3 2 1
13 3 9 1 4 2 1 I 2 2
1
Note. NED, no evidence of disease; DOD, dead of disease; AWD, alive with disease. a One patient died during operation and two patients died of other causes. b One patient died of the disease without any therapy instituted.
metastasis, VC of the female genital tract is a serious disease with a significant mortality. Totally, 23 patients (26.1%) died of the disease. Surgery, radiation, or a combination cured 63.6% (56 patients). Surgery as the only treatment in 55 patients cured 84% (46/.55). Radiation alone, in 13 patients, cured 23% (3/13) and the cure rate of combination therapy was 36% (7/19). Since spontaneous metastasis of VC of the female genital tract is extremely rare, a local excision of the tumor is a logical treatment. Wide local excision as the primary treatment has been advocated in several studies [4,10,22,30-321. In cases of large tumors or of recurrences, lsaacs [4] recommended regional lymph node dissection and Gallousis [33], in 1972, found that excision of the tumor and lymph node dissection were indicated in all cases until further knowledge of the metastatic rate of VC of the female genital tract was known. Anaplastic transformation of VC and subsequent lack of control of the tumor and metastasis have been shown to occur after radiation therapy [3,7,33,36-391. For this reason, radiation should be considered contraindicated in the treatment of vc. Local application of podophyllin [40], bleomycin therapy [7,41], and cryotherapy [lo] have all been ineffective. In conclusion, a verrucous tumor of the female genital tract should be removed with a margin of the surrounding healthy tissue. This is, in cases of VC a sufficient treatment and should enable the pathologist to make a precise diagnosis. Radiation should be contraindicated and bleomycin, local application of podophyllin, and cryosurgery are ineffective methods.
CASE REPORTS
433
REFERENCES 1. Ackerman, L. V. Verrucous carcinoma of the oral cavity, Surgery 23, 670-678 (1948). 2. Goethals, P. L., Harris, E. G., and Devine, K. D. Verrucous carcinoma of the oral cavity, Amer. J. Surg. 106, 845-851 (1963). 3. Kraus, F. T., and Perez-Mesa, C. Verrucous carcinoma-A clinical and pathologic study of 105 cases involving the oral cavity, larynx and genitalia, Cancer 19, 26-38 (1966). 4. Isaacs, J. H. Verrucous carcinoma of the female genital tract, Gynecol. Oncol. 4,259-269 (1976). 5. Powell, J. L., Franklin, E. W., Nickerson, J. F., and Burrell, M. D. Verrucous carcinoma of the female genital tract, Gynecol. Oncol. 6, 565-573 (1978). 6. Partridge, E. E., Murad, T., Shingleton, H. M., Austin, J. M., and Hatch, K. D. Verrucous lesions of the female genitalia. II: Verrucous carcinoma, Amer. J. Obstet. Gynecol. 137, 419424 (1980). 7. Vayrynen, M., Romppanen, T., Koskela, E., Castren, O., and Syrjanen, K. Verrucous squamous cell carcinoma of the female genital tract. Report of three cases and survey of the literature, Inc. J. Gynecol. Obstef. 19, 351-356 (1981). 8. Rando, R. E., Sedlacek, T. V., Hunt, J., Jenson, A. B., Kurman, R., and Lancaster, W. D. Verrucous carcinoma of the vulva associated with an unusual type 6 human papilloma virus, Obstet. Gynecol. 67, 7OS-75s (1986). 9. Selim, M. A., and Lankerani, M. R. Verrucous carcinoma of the vulva, J. Reprod. Med. 22, 93-96 (1979). 10. Stehman, F. B., Castaldo, T. W., Charles, E. H., and Lagasse, L. D. Verrucous carcinoma of the vulva, In?. J. Gynecol. Obstet. 17, 523-525 (1980). 11. Zaijman, J., Du, T., and Slabber, C. F. Verrucous carcinoma of the vulva, Brit. J. Obsret. Gynecol. 85, 74-76 (1978). 12. Andreasson, B., Bock, J. E., Strom, K. V., and Visfeldt, J. Verrucous carcinoma of the vulva1 region, Acta Obstet. Gynecol. Stand. 62, 183-186 (1983). 13. Demian, S. D. E., Bushkin, F. L., and Echevarria, R. A. Perineural invasion and anaplastic transformation of verrucous carcinoma, Cancer 32, 395-401 (1973). 14. Spratt, D. W., and Lee, S. C. Verrucous carcinoma of the cervix, Amer. J. Obstet. Gynecol. 129, 699-700 (1977). 15. Rorat, E., Benjamin, F., and Richart, R. M. Verrucous carcinoma of the cervix: A problem in diagnosis and management, Amer. J. Obsfet. Gynecol. 130, 851-853 (1978). 16. Yamasaki, M., Ueda, G., Sato, Y., Inoue, M., et al. A case of verrucous squamous cell carcinoma of the uterine cervix, Adv. Obstet. Gynecol. 29, 89-93 (1977). 17. Faaborg, L. L., Smith, M. L., and Newland, J. R. Case report. Uterine cervical and vaginal verrucous squamous cell carcinoma, Gynecol. Oncol. 8, 104-109 (1979). 18. Kashimura, M., Tsukamoto, N., Matsukuma, K., Matsuyama, T., Sugimori, H., and Taki, I. Verrucous carcinoma of the uterine cervix: Report of a case with follow-up of 6: years, Gynecol. Oncol. 19, 204-215 (1984). 19. Raheja, A., Katz, D. A., and Dermer, M. S. Verrucous carcinoma of the endocervix, Obstet. Gynecol. 62, 535-538 (1983). 20. Wood, W. G., Giustini, F. G., Sohn, S., and Aranda, R. R. Verrucous carcinoma of the vagina, South Med. J. 368-371 (1978). 21. Ramzy, I., Smoat, M. S., and Collins, J. A. Verrucous carcinoma of the vagina, Amer. J. Cfin. Parhol. 65, 644-653 (1976). 22. Japaze, H., Dinh, T. V., and Woodruff, T. D. Verrucous carcinoma of the vulva: Study of 24 cases, Obstet. Gynecol. 60, 462-466 (1982). 23. Sonck, C. E. Condylomata acuminata mit Ubergang in Karzinom, Z. Haur. Geschlechtskr. 46, 273-278 (1970). 24. Tiltman, A. J., and Nel, C. P. Verrucous carcinoma of the uterine cervix: A case report, Acta Cyrol. 27, 540-542 (1983). 25. Degefu, S., O’Quinn, A. G., Lacey, C. G., Merkel, M., and Barnard, D. E. Verrucous carcinoma of the cervix: Report of two cases and literature review, Gynecol. OncoL 25, 37-47 (1986).
434
ANDERSEN
AND
SORENSEN
26. Zachow, K. R., Ostrow, R. S., Bender, M., et al. Detection of human papilloma virus DNA in anogenital neoplasia, Nature 300, 771-775 (1982). 27. Durst, M., Gissmann, L., Ikenberg, H., et al. A papilloma virus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions, Proc. Nat/. Acad. Sci. USA 80, 3812-3816 (1983). 28. Okagaki, T. “Warty carcinoma” of the vulva: A probable implication of human papilloma virus as the causative agent, Lab. Invest. 44, 49A (1981). 29. Ubben, K., Krzyzek, R.. Ostrow, R., et al. Human papilloma virus DNA detected in two verrucous carcinomas, Clin. Res. 27, 538A (1979). 30. Andreasson, B. Invasive and intraepithelial neoplasia of the vulva, Dun. Med. Bull. 33, 184196 (1986).
31. Foye, G., Marsh, M. R., and Minkowitz, S. Verrucous carcinoma of the vulva,
Obstet.
Gynecoi.
34, 484-488 (1969). 32. Lucas, W. E., Benirschke, K., and Lebherz, T. B. Verrucous carcinoma of the female genital tract, Amer. .I. Obstet. Gynecol. 119, 435-440 (1974).
33. Gallousis, S. Verrucous carcinoma. Report of three vulvar cases and review of the literature, Obstet. Gynecol. 40, 502-507 (1972). 34. Jennings, R. H., and Barclay, D. L. Verrucous carcinoma of the cervix, Cancer 30, 430-434 (1972). 35. Prioleau, P. G., Santa Cruz, D. J., Meyer, J. S., and Bauer, W. C. Verrucous carcinoma. A light and electron microscopic, autoradiographic and immunofluorescence study, Cancer 45, 2849-2857 (1980). 36. Fonts, E. A., Greenlaw, R. H., Rush, B. F., ef al. Verrucous squamous cell carcinoma of the
oral cavity, Cancer 23, 152-160 (1969). 37. Perez-Mesa, C. A., Kraus, F. T., Evans, J. C., ef al. Anaplastic transformation in verrucous carcinoma of the oral cavity after radiation therapy, Radiology 86, 108-l 15 (1966). 38. Proffitt, S. D., Spooner, T. R., and Kosek, J. C. Origin of undifferentiated neoplasm from verrucous carcinoma of the oral cavity following irradiation, Cancer 26, 389-393 (1970). 39. van Nostrand, A. W. P., and Olofsson, J. Verrucous carcinoma of the larynx: A clinical and pathologic study of 10 cases, Cancer 30, 691-702 (1972). 40. Machacek, G. F., and Weakeley, D. R. Giant condyloma acuminata of Buschke and Lowenstein, Arch. Dermutol. 82, 41-57 (1960). 41. de Graff, J. and van der Harten, J. J. Ineffectiveness of bleomycin in verrucous carcinoma of the vulva, Eur. J. Obstet. Gynecol. Reprod. Biol. 5, 327-330 (1975).
ONCOLOGY
30, 427-434 (1988)
CASE REPORT Verrucous Carcinoma of the Female Genital Tract: Report of a Case and Review of the Literature ERIK SOGAARD ANDERSEN, *Departments
of Obstetrics
M.D.,*
AND
INGE MARIE SORENSEN,
and Gynecology and 7Department of Pathology, Section North, 8800 Viborg, Denmark
M.D.?
Aalborg
Hospital,
Received February 11, 1987 Verrucous carcinoma (VC) of the female genital tract is a rare lesion, primarily affecting postmenopausal women. A case of VC of the vulva is reported, bringing the total number of VC of the female genital tract to 89. VC is a slowly growing, locally “pushing” tumor with a rather benign histologic appearance, and the clinical and histologic characteristics are described on the basis of the present report and a review of the literature. The treatment of VC is still a matter of discussion. It seems logical to treat the tumor by wide local excision, taking the lack of proof of spontaneous metastasis into consideration. Radiation therapy should be contraindicated, and local application of podophyllin, bleomycin therapy, and cryosurgery are ineffective methods in the treatment of VC. o 1988 Academic press. IN.
INTRODUCTION
Ackerman [l], in 1948, described the clinical and histopathologic features of a distinct variant of epidermoid carcinoma of the oral cavity and designated the tumor verrucous carcinoma (VC). The female genital tract as a possible site of this tumor was suggested by Goethals et al. [2], and in 1966 Kraus and PerezMesa [3] reported the first two cases of VC of the female genital tract, one in the vagina and one in the vulva. According to the number of cases of VC of the female genital tract reported since 1966, it is a rare lesion. There still exist diagnostic difficulties and treatment is a matter of debate. The present paper presents a case of VC of the female genital tract, located in the vulva, and the literature is reviewed. The clinical and histologic features are described and the therapeutic aspects are discussed on the basis of the literature. CASE REPORT
An U-year-old woman, without previous gynecological disease, was admitted to a local hospital, April 29, 1985. She had complained of severe genital itching for 6 months. Examination revealed a 5 x 4 x 3.5 cm cauliflower-like tumor, 427 0090-8258/88 $1.50 Copyright Q 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.
428
ANDERSEN
AND
SORENSEN
originating in the left labium majus and involving the clitoral region. The tumor was excised. Microscopically, the diagnosis of a hyperkeratotic papilloma was made, but the possibility that the tumor was a verrucous carcinoma was considered. Six months later, January 7, 1986, the patient had a follow-up visit. The genital itching was still present. Physical examination showed a marked lichenization of the skin of the vulva region. Biopsies were taken, the microscopic examination showing severe keratinizing squamous dysplasia. The patient was then admitted to us. The biopsies were repeated, showing the same alterations of the epithelium; the previous specimens were reviewed and new deeper slides were cut from the original paraffin blocks. Microscopic jindings. The surface of the tumor was covered with papillary fronds composed of highly differentiated hyperkeratotic, parakeratotic, and acanthotic stratified squamous epithelium without major cellular polymorphism (Fig. 1). A few dyskeratotic cells and a few keratin pearls were seen in the deeper layer of the epithelium. A few islands of infiltrating squamous epithelium with nuclear atypia and keratinization were seen in the underlying inflammated stroma (Fig. 2). There was an abrupt transition between the lesion and the normal epithelium. In an adjacent area a focus of severe keratinizing squamous dysplasia was found (Fig. 3). Immunohistochemical investigation (rapid anti-bovine papilloma virus Type IBPVI-Dacopat California, #3580 lot #014 was used) revealed no human papilloma virus inclusions in the epithelium of the VC nor in the later biopsies. By electron microscopy the VC showed ultrastructural features similar to those of normal stratified squamous epithelium with easily identifiable tonofibrils and desmosomes. A simple vulvectomy was made, after repeated biopsies had shown a persisting severe keratinizing dysplasia. Microscopic examination of the vulvectomy preparation confirmed these alterations. Furthermore, minor areas of atrophic as well as hypertrophic dystrophic epithelial lesions were seen. There was no sign of persistence of recurrence of the VC. At the present time, 21 months after primary treatment, the patient is alive without any evidence of disease. DISCUSSION Verrucous carcinoma of the female genital tract is a rare lesion. A review of the literature revealed 88 cases previously reported [3-251. The location of the tumor and age characteristics are shown in Table 1. It is primarily a tumor of the postmenopausal age and involvement of the vulva and the cervix seems more common than involvement of the vagina. The patients with involvement of the uterine cervix seem to be slightly younger than patients with the tumor located in the vagina and the vulva. The etiology of VC of the female genital tract is unknown. In cases of verrucous carcinoma of the oral cavity and larynx, poor dental hygiene, tobacco chewing, and pipe smoking have been associated with the tumor [1,3,4,7]. Poor penile hygiene has been linked to the cases of VC of the penis [5,7] and poor perineal hygiene has been pointed out as a possible predisposing factor in cases of VC of the vulva [22]. Much evidence is accumulating indicating human papilloma
CASE
REPORTS
429
FIG. 1. Verrucous carcinoma. Papillary fronds of highly differentiated, hyperkeratotic, parakeratotic and acanthotic epithelium. (Hematoxylin - eosin, x 17.)
virus (HPV) as either the causative agent or a likely cofactor in the development of VC, since HPV has been found associated with this tumor [8,26-291. Further investigation is needed to make any final conclusions about the etiology of VC of the female genital tract. We were not able to demonstrate HPV inclusions. Macroscopically, VC is generally described as a cauliflower-like tumor [ 1,361. The color is greyish-white to red and the surface often shows signs of infection and ulceration. The size of the tumor may vary from less than 1 cm to more than 10 cm in diameter. The tumor is well-demarcated, growing slowly and pushing the surrounding tissue aside rather than infiltrating. As described by Kraus and Perez-Mesa [3]: “A slow but relentlessly expanding tumor.” Inflammatory enlargement of the regional lymph nodes is often present [5], and the tumor often grows around the lymph nodes rather than metastasizing to them
UA61.
430
ANDERSEN AND SORENSEN
FIG. 2. Verrucous carcinoma. A focus of invasion (arrow) in the underlying stroma. (Hematoxylin - eosin, X75.)
The frequency of metastasis to regional lymph nodes in cases of VC of the female genital tract is very low. Lymph node metastasis has been described in 5 cases [5,7,10,24,25], and in all cases the patients had been treated by primary radiation. No cases of spontaneous metastasis of VC of the female genital tract to regional lymph nodes have been reported. In two cases, histologically confirmed pulmonary metastasis of VC of the female genital tract has been reported [23,251. The tumor seems to be more aggressive in recurrent lesions [ 12,251.However, in most of these cases, the primary treatment had been radiation. There is generally agreement of the microscopic appearance of VC [1,4,6,30351. VC is a papillomatous tumor with a well-differentiated stratified squamous epithelium. The outer layers show pronounced hyperkeratosis and parakeratosis and in the deeper parts of the epithelium acanthosis is a main feature. There is only minimal polymorphism and mitotic figures are rare. Koilocytosis is a common finding. The lack of central connective tissue support is an important characteristic differentiating this tumor from benign condyloma. In VC fibrovascular cores are limited to the superficial parts of the tumor, unlike the condyloma in which the fibrovascular core extends from the deepest parts to the surface. This explains why superficially taken biopsies are of limited value in the cases of VC. To ensure a precise diagnosis, the whole tumor should be excised and presented to the pathologist. The basement membrane is usually intact, but occasionally, as in the present case, groups of invasive tumor cells are seen [23,35]. The stroma is characterized by a pronounced inflammatory response, the stroma containing
CASE
431
REPORTS
FIG. 3. Extended areas of severe keratinizing squamous dysplasia adjacent to the verrucous carcinoma. (Hematoxylin - eosin, x 96.)
lymphocytes, plasma cells, scattered eosiniphils, and occasionally micro-abscesses are formed. In a few cases, four patients in three reports [4,6,22], intraepithelial neoplasia has been described in areas adjacent to the tumor. In the present case, a severe keratinizing, squamous dysplasia was found in relation to the verrucous carcinoma and in the vulvectomy specimen. Electron microscopic studies show an appearance similar to that of normal stratified squamous epithelium [6,35]. Tonofibrils and desmosomes are easily identifiable. The treatment of verrucous carcinoma of the female genital tract is still a matter of discussion. The mode of treatment and the results obtained in previously reported cases are shown in Table 2. Despite the benign histologic appearance of VC, and the very low rate of TABLE 1 THE LOCATION
Location Vulva Cervix Vagina Total
OF VERRUCOUS CARCINOMAS OF THE FEMALE CHARACTERISTICS
GENITAL
TRACT AND THE AGE
Number
Mean age
>40 years (%)
48 30 10 88
58.3 51.0 56.4 55.6
39 (83) 21 (70) 9 (90) 69 (78)
432
ANDERSEN
AND
SORENSEN
TABLE 2 THE RESULTS OF TREATMENT OF VERRUCOUSCARCINOMA OF THE FEMALE GENITAL TRACT (PREVIOUSLY PUBLISHED CASES)
Vulva NED DOD AWD Cervix NED DOD AWD Vagina NED DOD AWD
No.
Surgery
Radiation
48’ 31 14 3 30 17 7” 3 10 8 2 0
34 28 5 1 14 12 2
1
7 6 I
Combination
1 11” 3 3 2 1
13 3 9 1 4 2 1 I 2 2
1
Note. NED, no evidence of disease; DOD, dead of disease; AWD, alive with disease. a One patient died during operation and two patients died of other causes. b One patient died of the disease without any therapy instituted.
metastasis, VC of the female genital tract is a serious disease with a significant mortality. Totally, 23 patients (26.1%) died of the disease. Surgery, radiation, or a combination cured 63.6% (56 patients). Surgery as the only treatment in 55 patients cured 84% (46/.55). Radiation alone, in 13 patients, cured 23% (3/13) and the cure rate of combination therapy was 36% (7/19). Since spontaneous metastasis of VC of the female genital tract is extremely rare, a local excision of the tumor is a logical treatment. Wide local excision as the primary treatment has been advocated in several studies [4,10,22,30-321. In cases of large tumors or of recurrences, lsaacs [4] recommended regional lymph node dissection and Gallousis [33], in 1972, found that excision of the tumor and lymph node dissection were indicated in all cases until further knowledge of the metastatic rate of VC of the female genital tract was known. Anaplastic transformation of VC and subsequent lack of control of the tumor and metastasis have been shown to occur after radiation therapy [3,7,33,36-391. For this reason, radiation should be considered contraindicated in the treatment of vc. Local application of podophyllin [40], bleomycin therapy [7,41], and cryotherapy [lo] have all been ineffective. In conclusion, a verrucous tumor of the female genital tract should be removed with a margin of the surrounding healthy tissue. This is, in cases of VC a sufficient treatment and should enable the pathologist to make a precise diagnosis. Radiation should be contraindicated and bleomycin, local application of podophyllin, and cryosurgery are ineffective methods.
CASE REPORTS
433
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