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Vulvodynia: an Indicator Or Even an Early Symptom of Vulvar Cancer Matthias Fischer, MD, Halle, Germany Wolfgang Ch

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Vulvodynia: an Indicator Or Even an Early Symptom of Vulvar Cancer Matthias Fischer, MD, Halle, Germany Wolfgang Ch Vulvodynia: An Indicator or Even an Early Symptom of Vulvar Cancer Matthias Fischer, MD, Halle, Germany Wolfgang Ch. Marsch, MD, Halle, Germany Vulvodynia is a symptom of chronic, painful vulvar discharge and reported that sexual intercourse was discomfort of multicausal origin. Vulvar cancer is no longer possible. A fibrinous, polycyclic ulcer with an underestimated cause of vulvodynia. Even early a diameter of 1.5 cm was found on the right labium stages of vulvar neoplasia can lead to aching minus. A similar ulcer with a diameter of 5 mm was lesions. Three cases of vulvar carcinoma eliciting found on the left labium minus. Because pain was persistent pain have been diagnosed within a extreme, speculum investigations were only possible 2-year period. In 2 of our case studies, women had after the administration of analgesic medication. antecedent periods of vulvar pruritus of long dura- Lymph nodes with diameters of up to 1 cm were pal- tion (5 and 20 years, respectively). We conclude pable at the groin. Both abdominal sonography and that early histologic examination of all visible vul- chest x-ray findings were normal. var lesions is necessary to exclude the presence Histologic examination showed squamous cell of malignant vulvar neoplasia. carcinoma of the vulva with moderate cell differenti- ation. The depth of invasion was 2 mm. The erythro- he International Society for the Study of cyte sedimentation rate was 20/37 mm. The Vulvar Disease defines vulvodynia as “chronic remaining laboratory values, including both white T vulvar discomfort, especially that characterized and red blood cell counts, were within the normal by the patient’s complaints of burning and sometimes range. Herpes simplex 1–serology values were ele- stinging, irritation, or rawness.”1 These leading symp- vated (IgG antibodies, 1197 IU/mL enzyme toms may have several nosologic classifications immunoassay; IgM antibodies, negative), and sero- (Table).2 Although vulvodynia is associated with con- logic parameters for herpes simplex 2, Epstein-Barr siderable suffering, most conditions are not life threat- virus, and cytomegalovirus were normal. Serologic ening. However, in a 2-year period we observed tests for syphilis and HIV infections were negative. 3 cases of vulvar cancer with symptomatic, persistent, Escherichia coli were cultured from an ulcer smear, but localized pain. Vulvar cancer is often miscalculated Candida albicans, chlamydia, herpes simplex types 1 and mismanaged by physicians and patients. and 2, and Neisseria gonorrhoeae were not detected. Following a diagnosis of vulvar cancer, radical vul- Case Reports vectomy with bilateral inguinal and femoral lymph Patient 1—A 45-year-old woman experienced chron- node excision was undertaken (classification: T3, ic vulvar discomfort for 5 years. Initially, she N2, MX, G1). complained of pruritus vulvae, which showed no sig- Patient 2—A 77-year-old woman suffered painful nificant improvement with local estradiol therapy. ulceration of the vestibulum vulvae for approxi- Twelve months prior to admission, she experienced mately 12 months. Initially, discomfort occurred only premenstrual burning that subsequently increased in during urination, but 4 weeks prior to hospital admis- intensity and was accompanied by a slowly growing sion, it developed into persistent burning pain, which erosion on the right labium minus. On examination, finally prompted her to seek medical intervention. no punch biopsy was taken because all of these symp- Herpes simplex infection was suspected, but systemic toms were thought to be caused by relapsing infec- treatment with acyclovir was unsuccessful. On admis- tions. The patient also had a brown vaginal sion, a painful, 3ϫ3-cm polycyclic ulcer with pro- truding lips was found on the left labium minus. Drs. Fischer and Marsch are from the Department of Dermatology, Because of the painful nature of the process, further Martin-Luther-University, Halle, Germany. Reprints: Matthias Fischer, MD, Department of Dermatology, gynecologic examination and swabs were only possi- Martin-Luther-University, Halle-Wittenberg, Ernst-Kromayer-Str. 5/6 ble after the administration of analgesic. A hard 06097, Halle/Saale, Germany. inguinal lymph node about the size of a walnut was VOLUME 67, MARCH 2001 235 VULVODYNIA ical attention. On examination, an exophytic Nosologic Classification 1ϫ0.7-cm tumor with a greasy yellow surface was 2 found immediately rostral to the upper commissure of Vulvodynia in the right labium minus. No inguinal lymph nodes • Cyclic vulvovaginitis were palpable. Abdominal sonography and chest radiography yielded normal results, and serology for •Vulvar vestibulitis syndrome syphilis was negative. Histologic examinations dis- closed a highly differentiated squamous cell carci- • Dysaesthetic vulvodynia noma of the vulva with a depth of invasion of •Vulvodynia due to local dermatoses 1.5 mm. A slightly elevated erythrocyte sedimenta- tion rate was the only pathologic laboratory value. •Vulvodynia due to other causes The patient underwent radical vulvectomy with bilateral inguinal and femoral lymph node excision. All lymph nodes were devoid of tumor cell infiltra- tion (FIGO classification: I, T1, N0, M0). Comment In the United States, the incidence of vulvar intraep- ithelial neoplasia (VIN) doubled to 2.1/100,000 between 1973 and 1987.3 In particular, VIN is becoming more prevalent in women younger than 35 years. Invasive vulvar cancer is a rare tumor that amounts to 1% of all malignant tumors in women4 and includes squamous cell carcinomas, basal cell car- cinomas, Paget disease, several forms of greater vestibular gland carcinoma, sarcomas, melanomas, and metastases.4,5 Pruritus vulvae is commonly the first symptom of Squamous cell carcinoma of the vulva in patient 2. vulvar neoplasia, although aching pain could become the leading symptom or the secondary palpable at the left side. Chest x-rays suggested a cir- symptom after local swelling.4 Pain is often con- cular focus in the left apex area, and abdominal sidered to be a late symptom of vulvar cancer, sonography was normal. Histologic examination particularly in cystic adenocarcinomas of the greater revealed a squamous cell carcinoma (pleomorphism vestibular gland.6,7 However, our observations from and cell complexes characterized by high desmosome patient 3 suggest that algesia could become populations)(Figure). A test for immunofluorescence symptomatic of vulvar cancer even at low depths of resulted in clear staining with cytokeratin LP34, invasion. Fischer et al,8 who discovered vulvar MNF116, and DEK-10. intraepithelial neoplasia in 5% of cases, supports The erythrocyte sedimentation rate was 15/34 mm, this hypothesis on the etiology of chronic vulvar and other laboratory values were within normal lim- complaints. Every fifth patient with VIN (1% of the its, except for slight hyperuricemia. Elevated IgG anti- whole collective) also suffered vulvodynia. The bodies against herpes simplex 1 (1442 IU/mL enzyme pathogenesis of this phenomenon has not yet been immunoassay) and herpes simplex 2 (1073 IU/mL clarified. Perineural invasion,9 which detrimentally enzyme immunoassay) were measured, and IgM anti- affects the intraepithelial nerve fibers of the introi- bodies and serology for syphilis and HIV were nega- tus vaginae, has been suggested. An involvement of tive. Proteus mirabilis and E coli were grown in cultures these free nerve endings may explain pain and pru- from the ulcer smear. ritus because they can be mediated by C-fiber The patient underwent radical vulvectomy with neurons and only differ in central neural modula- bilateral inguinal and femoral lymph node excision. tion.10,-12 This fact underlines the difficulty in Of the 14 lymph nodes, 9 were involved (classifica- distinguishing between pruritus vulvae and vulvo- tion: T3, N2, M0, G2). dynia in some cases because many patients experi- Patient 3—A 48-year-old woman suffered from ence both symptoms. This is also described by pruritus vulvae for about 20 years. In the 4 months McKay,13 though she clearly differentiates between prior to admission, a rapidly growing, painful vulvar the 2 symptoms.In our opinion, defining the leading tumor developed, which prompted her to seek med- CONTINUED ON PAGE 238 236 CUTIS® VULVODYNIA CONTINUED FROM PAGE 236 6. Bernstein SG, Voet RL, Lifshitz S, et al. Adenoid cystic or major symptom, especially for cutaneous causes of carcinoma of Bartholin’s gland: case report and review of chronic vulvar discomfort, might be the best idea. the literature. Am J Obstet Gynecol. 1983;147:385-390. It must be pointed out that vulvar cancer and VIN 7. Wheelock JB, Goplerud DR, Dunn LJ, et al. Primary car- are known,14,15 but not recognized, as causing these cinoma of the Bartholin gland: a report of ten cases. Ob- forms of vulvar complaints. Differential diagnoses of stet Gynecol. 1984;63:820-824. painful vulvar ulcers and erosions include infections 8. Fischer G, Spurrett B, Fischer A. The chronically symptom- due to herpes viruses (eg, herpes simplex, atic vulva: aetiology and management. Br J Obstet Gyn. cytomegalovirus), vesiculobullous autoimmune disor- 1995;102:773-779. ders, and ulcers due to systemic lupus erythematosus 9. Milchgrub S, Wiley EL, Vuitch F, et al. The tubular vari- or Behçet’s syndrome.15,16 ant of adenoid cystic carcinoma of the Bartholin’s gland. Our cases show that vulvodynia may be a leading Am J Clin Pathol. 1994;101:204-208. and possible early sign of vulvar cancer. Early histo- 10. Hilliges M, Falconer C, Ekman-Ordeberg G, et al. Inner- logic examination in all cases of epithelial abnormal- vation of the human vaginal mucosa as revealed by PGP ities, especially erosive or ulcerative lesions at the 9.5 immunohistochemistry. Acta Anat (Basel). 1995;153: vulva, should be mandatory to improve the prognoses 119-126. of the patients. 11. Iggo A, Andres KH. Morphology of cutaneous receptors. Annu Rev Neurosci. 1982;5:1-31. REFERENCES 12. Greaves MW. Anti-itch treatments: do they work? Skin 1. Burning vulvar syndrome: report of the ISSVD task force. Pharmacol. 1997;10:225-229.
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