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A rare case of vulvar endometriosis in an adolescent girl
CASE REPORT A rare case of vulvar endometriosis in an adolescent girl Aimee D. Eyvazzadeh, M.D.,a Yolanda R. Smith, M.D., M.S.,a Richard Lieberman, M.D.,a,b and Elisabeth H. Quint, M.D.a a
Department of Obstetrics and Gynecology and b Department of Pathology, School of Medicine, University of Michigan, Ann Arbor, Michigan
Objective: To describe a case of vulvar endometriosis in a teenager after a history of vulvar ulcers in the same location. Design: Case report. Setting: University medical center. Patient(s): A 13-year-old girl with a history of vulvar ulcers. Main Outcome Measure(s): None. Result(s): A 13-yr-old female presented with painful, open vulvar ulcerations on the inner side of her labia minora. Biopsy revealed dermatitis with ulceration. One year later she noted an ulcer and blood in her undergarments. Biopsy results were consistent with endometriosis. Five years later, the lesions persisted and bled during menses. A bilateral labial excision was performed. Pathology again revealed endometriosis. Conclusion(s): Vulvar endometriosis is extremely unusual. This rare case of vulvar endometriosis in the same location as a previous vulvar ulcer is most likely due to ectopic transplantation of endometrial cells during a menstrual cycle. Excision is considered definitive treatment. (Fertil Steril 2009;91:929.e9–e11. 2009 by American Society for Reproductive Medicine.) Key Words: Vulvar endometriosis, adolescent, vulvar ulcer
Endometriosis, characterized by growth of endometrial glands and stroma outside the endometrium, can be found in abnormal locations both within and outside the pelvis. Vulvar involvement of endometriosis, not associated with episiotomies, is extremely rare. We present a case of a 13-year-old girl who presented with vulvar ulcers and was later diagnosed with vulvar endometriosis in the same location.
CASE REPORT A 13-year-old girl presented with a 1-week history of painful vulvar ulcers while camping in Alaska with her family. She underwent menarche 4 months before presentation. She was seen and treated at an outside hospital for presumed herpes simplex virus with acyclovir and pain medication. Her viral cultures returned negative, and the ulcers persisted. She was referred to our institution for further evaluation. The patient was seen in our clinic and was too uncomfortable to tolerate a vulvar examination. A review of systems was otherwise negReceived April 14, 2008; revised October 9, 2008; accepted October 17, 2008. Y.R.S.’s spouse or partner is on the speakers’ bureau of Eli Lilly and Forest Laboratories. R.L. is a consultant for Science and Technology International. A.D.E. has nothing to disclose. E.H.Q. has nothing to disclose. Reprint requests to: Elisabeth H. Quint, M.D., Department of Obstetrics and Gynecology, University of Michigan, 1100 E. Medical Center Drive, Ann Arbor, MI 48105 (FAX: 734-647-9727; E-mail: [email protected]).
0015-0282/09/$36.00 doi:10.1016/j.fertnstert.2008.10.026
ative. No systemic symptoms were noted on initial presentation. A physical examination did not reveal any other lesions on her body or in her mouth. She was then taken to the operating room for an examination under anesthesia; two 3 4-cm vulvar ulcerations were noted on the inner aspect of her labia minora bilaterally (Fig. 1A). Significant edema was noted. Biopsy revealed suppurative superficial and deep dermatitis with ulceration. Direct immunofluorescence examination of the skin biopsy specimen using monospecific fluorescein isothiocyanate–conjugated antihuman IgG, -A, -M, -C3, and fibrin showed no immune deposition, which ruled out Behcxet’s disease. Results from all viral cultures were negative, and her ulcers resolved. One year later, at age 14 years, she noted a painless vulvar lesion, as well as blood on her underwear. She was taken to the operating room for the second time, where an examination under anesthesia was performed. Physical examination revealed a 1.5 1.5-cm, red, raised area on the inside of the left labium minora. Cultures and a biopsy were performed. The biopsy revealed endometriosis arising in vulvar epithelium, with extensive underlying acute and chronic inflammation and reactive lymphoid hyperplasia, estrogen and P receptor positive. CD10 staining was used in this case because the inflammatory infiltrate obscured our ability to see the endometrial stroma (Fig. 1B). CD10 is a cell-surface metalloendopeptidase expressed in normal and ectopic
Fertility and Sterility Vol. 91, No. 3, March 2009 Copyright ª2009 American Society for Reproductive Medicine, Published by Elsevier Inc.
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FIGURE 1 (A) At age 13 years, bilateral ulcerative lesions are noted on the inside of the labium minora, as well as significant edema of the clitoris and labia. (B) CD10 staining demonstrates condensation of endometrial stroma around the glands. (C) At age 20 years, a 2.0 2.0-cm lesion on the inner aspect of the left labium minora and a 3-mm lesion on the medial aspect of the right labium minora are seen.
Eyvazzadeh. Vulvar endometriosis in an adolescent. Fertil Steril 2009.
endometrial stroma. CD10 immunohistochemistry increases the sensitivity of hematoxylin and eosin–based histologic diagnosis of endometriosis by improving the recognition of the ectopic stromal cells. Results of herpes simplex virus culture were again negative. The patient was relatively asymptomatic, and expectant management was chosen. Five years later, at age 20 years, the patient presented with the vulvar lesion slightly larger in size. She reported that the lesion occasionally bled during menses and requested surgical excision. A 2 2-cm lesion on the inner aspect of the left labium minora and a 3-mm lesion on the medial aspect of the right labium minora were present (Fig. 1C). A left labial wide local excision and right labial excision were performed. Pathologic evaluation again identified endometriosis in both lesions. No recurrence has occurred as of 6 months’ followup after surgery. DISCUSSION This case of vulvar endometriosis in an adolescent demonstrates ulcerations of unknown etiology in a 13-year-old, with the development of endometriosis in the same locations 1 year later. Expectant management was chosen until the patient desired definitive surgical management at age 20 years. Vulvar ulcers can be caused by infection, malignancy, or certain systemic diseases. In the absence of other clinical diagnoses, lesions may be idiopathic. The initial ulceration in this patient was never diagnosed with an infectious etiology, 929.e10
Eyvazzadeh et al.
because results from all cultures and biopsies were negative. In addition, the ulcers were tender and resolved spontaneously. In teenagers aphthous ulcers may present with all of these clinical features (1). There are several theories regarding the pathogenesis of endometriosis: ectopic transplantation of endometrial tissue, coelomic metaplasia, and vascular dissemination (2). Ectopic transplantation is found when the endometrial cells implant directly in other areas (e.g., retrograde flow from the fallopian tubes, leading to peritoneal implants). The theory of coelomic metaplasia involves metaplasia of cells lining the pelvic peritoneum resulting in endometriosis and explains the development of endometriosis in the ovaries, peritoneum, and urinary bladder. Distant locations of endometriosis, such as the pleura or pericardium, are thought to be due to vascular dissemination, with endometrial cells entering the blood and lymphatic system. In this unique case of vulvar endometriosis after ulceration, it is plausible that the origin of the vulvar endometriosis was ectopic transplantation in the area where the initial ulceration was seen. Because the initial biopsy was free of endometriosis, the subsequent finding of endometriosis may be secondary to endometrium from menstrual tissue implanting in the open ulcerative lesions. Alternatively, the initial biopsy may have missed the glandular tissue because of the extensive inflammation present, although no bleeding was ever noted with the ulceration. Only two other cases of vulvar endometriosis in adolescents have been published. In one case, a 12-year-old postmenarchal girl presented with a vulvar hematoma that resolved with conservative management and 2 years later developed a vulvar mass in the same location, which was subsequently excised and found to be an endometrioma (3). In a second report a 15-year-old girl presented complaining of a painful tender mass occurring monthly for 6 months in her left labium majora (4), possibly explained by vascular or lymphatic dissemination, given that there was no trauma described preceding this mass. Other cases of vulvar endometriosis reported in the literature involve endometriosis in vulvar scars such as episiotomy scars (5). The incidence of perineal endometriosis after episiotomy has been reported as 0.32% (6). In such cases, excision of suspected vulvar endometriosis is suggested as the definite treatment. This case raises interesting questions regarding endometriosis. First, with vulvar lesions being fairly common, why would implantation of menstrual endometrium occur so rarely? Perhaps defective immunosurveillance played a role in this case and allowed for the survival of the ectopic endometrial tissue (7). For endometriosis to develop, a complex network of locally produced cytokines must modulate the growth and inflammatory behavior of ectopic endometrial implants. Proinflammatory proteins from the endometriotic lesions and associated immune cells then contribute to the enhanced inflammatory reaction associated with endometriosis, which contributes to the survival of these lesions. Another
Vulvar endometriosis in an adolescent
Vol. 91, No. 3, March 2009
issue is whether this young patient is at risk for endometriosis in other locations. In a related scenario, one adult patient with endometriosis in a Bartholin’s gland was found to have some minimal intraperitoneal endometriosis as well (8). In summary, a rare case of vulvar endometriosis in a teenager that arose in the area of previous vulvar ulcers is presented. Ectopic transplantation of endometrial cells during menstruation is suspected, and excision is the definitive treatment. REFERENCES 1. Huppert JS, Gerber MA, Deitch HR, Mortensen JE, Staat MA, Adams Hillard PJ. Vulvar ulcers in young females: a manifestation of aphthosis. J Pediatr Adolesc Gynecol 2006;19:195–204.
Fertility and Sterility
2. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril 1997;68:585–96. 3. Katz Z, Goldchmit R, Blickstein I. Post-traumatic vulvar endometriosis. Eur J Pediatr Surg 1996;6:241–2. 4. Su HY, Chen WH, Chen CH. Extra-pelvic endometriosis presenting as a vulvar mass in a teenage girl. Int J Gynaecol Obstet 2004;87:252–3. 5. Gunes M, Kayikcioglu F, Ozturkoglu E, Haberal A. Incisional endometriosis after cesarean section, episiotomy and other gynecologic procedures. J Obstet Gynaecol Res 2005;31:471–5. 6. Wang HB, Zhu L, Lang JH, Liu ZF, Sun DW, Leng JH, et al. Clinical analysis of 30 patients with perineal endometriosis. Zhonghua Yi Xue Za Zhi 2007;87:1181–3. 7. Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril 2001;75:1–10. 8. Gocmen A, Inaloz HS, Sari I, Inaloz SS. Endometriosis in the Bartholin gland. Eur J Obstet Gynecol Reprod Biol 2004;114:110–1.
929.e11
Department of Obstetrics and Gynecology and b Department of Pathology, School of Medicine, University of Michigan, Ann Arbor, Michigan
Objective: To describe a case of vulvar endometriosis in a teenager after a history of vulvar ulcers in the same location. Design: Case report. Setting: University medical center. Patient(s): A 13-year-old girl with a history of vulvar ulcers. Main Outcome Measure(s): None. Result(s): A 13-yr-old female presented with painful, open vulvar ulcerations on the inner side of her labia minora. Biopsy revealed dermatitis with ulceration. One year later she noted an ulcer and blood in her undergarments. Biopsy results were consistent with endometriosis. Five years later, the lesions persisted and bled during menses. A bilateral labial excision was performed. Pathology again revealed endometriosis. Conclusion(s): Vulvar endometriosis is extremely unusual. This rare case of vulvar endometriosis in the same location as a previous vulvar ulcer is most likely due to ectopic transplantation of endometrial cells during a menstrual cycle. Excision is considered definitive treatment. (Fertil Steril 2009;91:929.e9–e11. 2009 by American Society for Reproductive Medicine.) Key Words: Vulvar endometriosis, adolescent, vulvar ulcer
Endometriosis, characterized by growth of endometrial glands and stroma outside the endometrium, can be found in abnormal locations both within and outside the pelvis. Vulvar involvement of endometriosis, not associated with episiotomies, is extremely rare. We present a case of a 13-year-old girl who presented with vulvar ulcers and was later diagnosed with vulvar endometriosis in the same location.
CASE REPORT A 13-year-old girl presented with a 1-week history of painful vulvar ulcers while camping in Alaska with her family. She underwent menarche 4 months before presentation. She was seen and treated at an outside hospital for presumed herpes simplex virus with acyclovir and pain medication. Her viral cultures returned negative, and the ulcers persisted. She was referred to our institution for further evaluation. The patient was seen in our clinic and was too uncomfortable to tolerate a vulvar examination. A review of systems was otherwise negReceived April 14, 2008; revised October 9, 2008; accepted October 17, 2008. Y.R.S.’s spouse or partner is on the speakers’ bureau of Eli Lilly and Forest Laboratories. R.L. is a consultant for Science and Technology International. A.D.E. has nothing to disclose. E.H.Q. has nothing to disclose. Reprint requests to: Elisabeth H. Quint, M.D., Department of Obstetrics and Gynecology, University of Michigan, 1100 E. Medical Center Drive, Ann Arbor, MI 48105 (FAX: 734-647-9727; E-mail: [email protected]).
0015-0282/09/$36.00 doi:10.1016/j.fertnstert.2008.10.026
ative. No systemic symptoms were noted on initial presentation. A physical examination did not reveal any other lesions on her body or in her mouth. She was then taken to the operating room for an examination under anesthesia; two 3 4-cm vulvar ulcerations were noted on the inner aspect of her labia minora bilaterally (Fig. 1A). Significant edema was noted. Biopsy revealed suppurative superficial and deep dermatitis with ulceration. Direct immunofluorescence examination of the skin biopsy specimen using monospecific fluorescein isothiocyanate–conjugated antihuman IgG, -A, -M, -C3, and fibrin showed no immune deposition, which ruled out Behcxet’s disease. Results from all viral cultures were negative, and her ulcers resolved. One year later, at age 14 years, she noted a painless vulvar lesion, as well as blood on her underwear. She was taken to the operating room for the second time, where an examination under anesthesia was performed. Physical examination revealed a 1.5 1.5-cm, red, raised area on the inside of the left labium minora. Cultures and a biopsy were performed. The biopsy revealed endometriosis arising in vulvar epithelium, with extensive underlying acute and chronic inflammation and reactive lymphoid hyperplasia, estrogen and P receptor positive. CD10 staining was used in this case because the inflammatory infiltrate obscured our ability to see the endometrial stroma (Fig. 1B). CD10 is a cell-surface metalloendopeptidase expressed in normal and ectopic
Fertility and Sterility Vol. 91, No. 3, March 2009 Copyright ª2009 American Society for Reproductive Medicine, Published by Elsevier Inc.
929.e9
FIGURE 1 (A) At age 13 years, bilateral ulcerative lesions are noted on the inside of the labium minora, as well as significant edema of the clitoris and labia. (B) CD10 staining demonstrates condensation of endometrial stroma around the glands. (C) At age 20 years, a 2.0 2.0-cm lesion on the inner aspect of the left labium minora and a 3-mm lesion on the medial aspect of the right labium minora are seen.
Eyvazzadeh. Vulvar endometriosis in an adolescent. Fertil Steril 2009.
endometrial stroma. CD10 immunohistochemistry increases the sensitivity of hematoxylin and eosin–based histologic diagnosis of endometriosis by improving the recognition of the ectopic stromal cells. Results of herpes simplex virus culture were again negative. The patient was relatively asymptomatic, and expectant management was chosen. Five years later, at age 20 years, the patient presented with the vulvar lesion slightly larger in size. She reported that the lesion occasionally bled during menses and requested surgical excision. A 2 2-cm lesion on the inner aspect of the left labium minora and a 3-mm lesion on the medial aspect of the right labium minora were present (Fig. 1C). A left labial wide local excision and right labial excision were performed. Pathologic evaluation again identified endometriosis in both lesions. No recurrence has occurred as of 6 months’ followup after surgery. DISCUSSION This case of vulvar endometriosis in an adolescent demonstrates ulcerations of unknown etiology in a 13-year-old, with the development of endometriosis in the same locations 1 year later. Expectant management was chosen until the patient desired definitive surgical management at age 20 years. Vulvar ulcers can be caused by infection, malignancy, or certain systemic diseases. In the absence of other clinical diagnoses, lesions may be idiopathic. The initial ulceration in this patient was never diagnosed with an infectious etiology, 929.e10
Eyvazzadeh et al.
because results from all cultures and biopsies were negative. In addition, the ulcers were tender and resolved spontaneously. In teenagers aphthous ulcers may present with all of these clinical features (1). There are several theories regarding the pathogenesis of endometriosis: ectopic transplantation of endometrial tissue, coelomic metaplasia, and vascular dissemination (2). Ectopic transplantation is found when the endometrial cells implant directly in other areas (e.g., retrograde flow from the fallopian tubes, leading to peritoneal implants). The theory of coelomic metaplasia involves metaplasia of cells lining the pelvic peritoneum resulting in endometriosis and explains the development of endometriosis in the ovaries, peritoneum, and urinary bladder. Distant locations of endometriosis, such as the pleura or pericardium, are thought to be due to vascular dissemination, with endometrial cells entering the blood and lymphatic system. In this unique case of vulvar endometriosis after ulceration, it is plausible that the origin of the vulvar endometriosis was ectopic transplantation in the area where the initial ulceration was seen. Because the initial biopsy was free of endometriosis, the subsequent finding of endometriosis may be secondary to endometrium from menstrual tissue implanting in the open ulcerative lesions. Alternatively, the initial biopsy may have missed the glandular tissue because of the extensive inflammation present, although no bleeding was ever noted with the ulceration. Only two other cases of vulvar endometriosis in adolescents have been published. In one case, a 12-year-old postmenarchal girl presented with a vulvar hematoma that resolved with conservative management and 2 years later developed a vulvar mass in the same location, which was subsequently excised and found to be an endometrioma (3). In a second report a 15-year-old girl presented complaining of a painful tender mass occurring monthly for 6 months in her left labium majora (4), possibly explained by vascular or lymphatic dissemination, given that there was no trauma described preceding this mass. Other cases of vulvar endometriosis reported in the literature involve endometriosis in vulvar scars such as episiotomy scars (5). The incidence of perineal endometriosis after episiotomy has been reported as 0.32% (6). In such cases, excision of suspected vulvar endometriosis is suggested as the definite treatment. This case raises interesting questions regarding endometriosis. First, with vulvar lesions being fairly common, why would implantation of menstrual endometrium occur so rarely? Perhaps defective immunosurveillance played a role in this case and allowed for the survival of the ectopic endometrial tissue (7). For endometriosis to develop, a complex network of locally produced cytokines must modulate the growth and inflammatory behavior of ectopic endometrial implants. Proinflammatory proteins from the endometriotic lesions and associated immune cells then contribute to the enhanced inflammatory reaction associated with endometriosis, which contributes to the survival of these lesions. Another
Vulvar endometriosis in an adolescent
Vol. 91, No. 3, March 2009
issue is whether this young patient is at risk for endometriosis in other locations. In a related scenario, one adult patient with endometriosis in a Bartholin’s gland was found to have some minimal intraperitoneal endometriosis as well (8). In summary, a rare case of vulvar endometriosis in a teenager that arose in the area of previous vulvar ulcers is presented. Ectopic transplantation of endometrial cells during menstruation is suspected, and excision is the definitive treatment. REFERENCES 1. Huppert JS, Gerber MA, Deitch HR, Mortensen JE, Staat MA, Adams Hillard PJ. Vulvar ulcers in young females: a manifestation of aphthosis. J Pediatr Adolesc Gynecol 2006;19:195–204.
Fertility and Sterility
2. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril 1997;68:585–96. 3. Katz Z, Goldchmit R, Blickstein I. Post-traumatic vulvar endometriosis. Eur J Pediatr Surg 1996;6:241–2. 4. Su HY, Chen WH, Chen CH. Extra-pelvic endometriosis presenting as a vulvar mass in a teenage girl. Int J Gynaecol Obstet 2004;87:252–3. 5. Gunes M, Kayikcioglu F, Ozturkoglu E, Haberal A. Incisional endometriosis after cesarean section, episiotomy and other gynecologic procedures. J Obstet Gynaecol Res 2005;31:471–5. 6. Wang HB, Zhu L, Lang JH, Liu ZF, Sun DW, Leng JH, et al. Clinical analysis of 30 patients with perineal endometriosis. Zhonghua Yi Xue Za Zhi 2007;87:1181–3. 7. Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril 2001;75:1–10. 8. Gocmen A, Inaloz HS, Sari I, Inaloz SS. Endometriosis in the Bartholin gland. Eur J Obstet Gynecol Reprod Biol 2004;114:110–1.
929.e11