Are You Confident of the Diagnosis?
Pelvic endometriosis affects around 10% of females of reproductive age. Involvement typically includes the ovaries, fallopian tubes, uterosacral ligaments, rectovaginal septum and peritoneum. Less than 15% of patients with pelvic endometriosis have coexistent extrapelvic endometriosis, which is most commonly found either intraabdominally (intestinal, renal, and appendiceal involvement) or in the lung (catamenial pneumothorax).
Rarely, patients will present with cutaneous endometriosis, also known as cutaneous endo, endometrioma, or ectopic endometrial tissue. Cutaneous endometriosis can be subdivided into two forms – cicatricial (arising in abdominopelvic scars particularly after procedures involving the uterus) and spontaneous (typically arising in the umbilicus), which are seen in 1% and <1%, respectively, of patients with extrapelvic endometriosis.
What you should be alert for in the history
Patients with cutaneous endometriosis present with history of a slowly growing nodule with cyclical bleeding or tenderness related to the menstrual cycle. They will also typically (though not always) have signs or symptoms of pelvic endometriosis, including history of infertility, dysmenorrhea, menorrhagia, peri-menstrual spotting, dyspareunia, dysuria or cyclical painful bowel movements.
Most patients with cutaneous endometriosis will have a history of abdominopelvic surgery, including cesarean section, episiotomy, hysterectomy, and laparoscopic or open abdominal surgery. Patients with history of surgeries involving the uterus are particularly at risk. The time between the surgery and the development of cutaneous endometriosis has been reported to be between 8 months and 19 years.
Characteristic findings on physical examination
Physical examination reveals a soft flesh-colored to darkly pigmented nodule usually located either at the umbilicus or within an abdominopelvic scar. At times the nodules may have hemorrhagic crust or active bleeding and may be tender. In rarer cases, cutaneous endometriosis may present as multiple discrete erythematous papules or plaques or as a primary nodule surrounded by smaller papules.
Expected results of diagnostic studies
The gold-standard diagnostic test for cutaneous endometriosis is excisional biopsy and pathologic examination. Histopathology reveals ectopic irregular glandular spaces with surrounding loose fibromyxoid stroma resembling uterine endometrial stroma. Extravasated erythrocytes and hemosiderin-laden macrophages in the dermal stroma correspond to recurrent bleeding (Figure 1, Figure 2).
The lining of the glandular spaces is phasic, revealing either a proliferative phase (with tortuous pseudostratified glands) or a secretory phase (with decapitation secretion). Interestingly the phase seen in ectopic endometriosis is often poorly correlated with the menstrual cycle. Dermoscopy may reveal homogeneous red pigmentation with small globules known as “red atolls,” which have been histopathologically found to be irregular glands containing red blood cells.
The differential diagnosis of cutaneous endometriosis includes malignant lesions such as amelanotic melanoma, cutaneous metastases from intraabdominal cancer (Sister Mary Joseph nodule) or extraabdominal cancer, and keratinocyte carcinomas (basal cell cancer, squamous cell cancer or keratoacanthoma). Benign tumors including pyogenic granuloma, hemangioma, and cysts (dermoid cyst or epidermal inclusion cyst) may also be included. Cicatricial endometriosis can have a clinical appearance similar to a keloid or hypertrophic scar, and spontaneous endometriosis may mimic an umbilical hernia or omphalocele.
Who is at Risk for Developing this Disease?
The epidemiology of cutaneous endometriosis is similar to that of pelvic endometriosis including females of reproductive age, though there have been reports in postmenopausal women as well. Typically, though not always, patients will have coexistent pelvic endometriosis. Patients with a history of abdominopelvic surgery, especially involving the uterus, are at increased risk of cicatricial cutaneous endometriosis.
What is the Cause of the Disease?
Pelvic endometriosis is the implantation of viable endometrial cells from the uterine cavity into pelvic tissue, thought to be most likely due to reflux menstruation through the fallopian tubes. Cicatricial cutaneous endometriosis is most likely similarly caused by the seeding and implantation of viable endometrial cells into the skin during surgery. The source of the viable endometrial cells is either the uterine cavity itself in patients undergoing pelvic surgery that disrupts the uterus or the peritoneal cavity in patients with coexistent pelvic endometriosis.
The pathophysiology of spontaneous endometriosis is not as well understood, with leading hypothesis including either lymphangitic or hematogenous spread of viable endometrial cells or the development from stem cells of the mesoderm.
Systemic Implications and Complications
Patients with cutaneous endometriosis will typically, though not always, have either known or undiagnosed pelvic endometriosis. Work-up should include a thorough reproductive history including ability or inability to conceive as well as a targeted review of systems looking for symptoms of pelvic endometriosis (including dysmenorrhea, menorrhagia, peri-menstrual spotting, dyspareunia, dysuria and cyclical painful bowel movements).
Physical examination should include an abdominal examination as well as a thorough pelvic examination. Imaging studies including pelvic or abdominal ultrasound or MRI may be beneficial to assist in the diagnosis of pelvic endometriosis, though the definitive diagnostic test as well as treatment option is laparoscopy to evaluate for and ablate endometrial implants and intrapelvic or intraabdominal scar tissue.
Hormonal treatment in the form of gonadotropin-releasing hormone agents, danazol, oral contraceptive pills or progestins may also be used for symptomatic relief. Symptoms of pelvic endometriosis typically will resolve after menopause.
Treatment options are summarized in Table I.
|Medical treatment – topical||—|
|Medical treatment – systemic||Hormonal treatment|
|Surgical treatment||Surgical excision|
Optimal Therapeutic Approach for this Disease
Because of a small risk of malignant transformation of cutaneous endometriosis, the treatment of choice is complete surgical excision. In patients with very large or painful lesions of cutaneous endometriosis, there have been reports of preoperative hormonal treatment, typically for 3-4 months with anti-gonadotropin agents such as gonadotropin-releasing hormone agonists (eg, leuprolide 3.75mg IM monthly), aromatase inhibitors (eg, anastrozole 1mg orally daily) or danazol (100-400mg orally twice daily)to reduce the size of cutaneous endometriosis and for pain relief prior to excision.
The risk of recurrence after excision is very low. Any recurrence should raise suspicion for malignant degeneration and an excisional biopsy should be performed without delay.
Recurrence after surgical excision of cutaneous endometriosis is extremely rare, and any recurrence should signal a work-up for malignant degeneration of cutaneous endometriosis. Though rare, malignant transformation has been reported up to 39 years after development of cutaneous endometriosis, which highlights the need for prompt and complete surgical excision of cutaneous endometriosis as well as for long-term follow-up. Patients should be advised that any signs or symptoms of recurrence should immediately be brought to the attention of their health-care provider.
Unusual Clinical Scenarios to Consider in Patient Management
Rare cases of malignant transformation of cutaneous endometriosis have been reported. Risk factors of malignant degeneration include delay of surgical excision of primary lesion of cutaneous endometriosis, failure to completely excise the affected tissue, clinical recurrence at site of previous excision, and possibly estrogen stimulation. Malignant transformation has been reported to be delayed from 3-39 years after the development of primary cutaneous endometriosis, highlighting the need for long-term follow-up of patients with cutaneous endometriosis.
Clinical signs and symptoms that should raise concern for malignant transformation are clinical recurrence, rapid growth, increasing pain and regional lympadenopathy. The diagnosis of malignant transformation is accomplished with excisional biopsy and fine-needle aspiration or biopsy of clinically enlarged lymph nodes. The most common diagnoses of malignant transformation include endometrioid carcinoma, sarcoma, clear cell adenocarcinoma, and mucinous or serous carcinoma.
The pathophysiology of malignant transformation is not well understood but is thought to be due to a combination of estrogen stimulation and slow evolution from dysplasia to carcinoma. Due to this risk of malignant transformation, lesions of primary endometriosis should undergo prompt and complete surgical excision whenever possible.
What is the Evidence?
Bulun, SE. “Endometriosis”. N Engl J Med. vol. 360. 2009. pp. 268-79. (Comprehensive review of pelvic endometriosis.)
Elm, MK, Twede, JV, Turiansky, GW. “Primary cutaneous endometriosis of the umbilicus: a case report”. Cutis. vol. 81. 2008. pp. 124-6. (Case report and brief review of umbilical cutaneous endometriosis.)
Scholefield, HJ, Sajjad, Y, Morgan, PR. “Cutaneous endometriosis and its association with caesarean section and gynaecological procedures”. J Obstet Gynaecol. vol. 22. 2002. pp. 553-4. (Review of cicatricial cutaneous endometriosis.)
vonStemm, AMR, Meigel, WN, Scheidel, P, Gocht, A. “Umbilical endometriosis”. J European Acad Dermatol Venerol. vol. 12. 1999. pp. 30-32. (Case report and brief discussion of umbilical cutaneous endometriosis.)
Kazakov, DV, Ondic, O, Zamecnik, M, Shelekhova, KV, Mukensnabl, P, Hes, O. “Morphological variations of scar-related and spontaneous endometriosis of the skin and superficial soft tissue: A study of 71 cases with emphasis on atypical features and types of mullerian differentiations”. J Am Acad Dermatol. vol. 57. 2007. pp. 134-46. (Case series of patients with spontaneous and cicatricial cutaneous endometriosis with focus on histopathological findings.)
DeGiorgi, V, Massi, D, Mannone, F, Stante, M, Carli, P. “Cutaneous endometriosis: non-invasive analysis by epiluminescence microscopy”. Clin Exp Dermatol. vol. 28. 2003. pp. 315-17. (Case report and dermoscopic findings of a patient with umbilical cutaneous endometriosis.)
Elder, DE, Elenitsas, R, Ragsdale, BD, Elder, DE, Elenitsas, R, Jaworsky, C, Johnson, B. “Tumors of the epidermal appendages – cutaneous endometriosis”. Lever’s histopathology of the skin. 1997. pp. 796-7. (Discussion of histopathologic findings seen in cutaneous endometriosis.)
Choi, SW, Lee, HN, Kang, SJ, Kim, HO. “A case of cutaneous endometriosis developed in postmenopausal woman receiving hormonal replacement”. J Am Acad Dermatol. vol. 41. 1999. pp. 327-9. (Case report of cutaneous endometriosis with an atypical presentation.)
Chene, G, Darcha, C, Dechelotte, P, Mage, G, Canis, M. “Malignant degeneration of perineal endometriosis in episiotomy scar, case report and review of the literature”. Int J of Gynecol Cancer. vol. 17. 2007. pp. 709-14. (Case report of malignant degeneration of cicatricial cutaneous endometriosis with discussion of management from an obstetrics and gynecologic standpoint.)
Kang, SK, Lee, MW, Choi, JH, Sung, KJ, Moon, KC, Koh, JK. “Cutaneous endometriosis: a combination of medical and surgical treatment”. J Dermatol Treatment. vol. 13. 2002. pp. 89-92. (Review of treatment and management strategies for patients with cutaneous endometriosis.)
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