Cutaneous Endometriosis

Etiology

Cutaneous endometriosis can be divided into primary cutaneous endometriosis and secondary cutaneous endometriosis. The etiology of primary cutaneous endometriosis is unclear and is known to occur spontaneously. The cause of secondary cutaneous endometriosis is assumed to occur due to seeding after procedures relating to abdominal or pelvic surgery resulting in the implantation of endometrial tissue into the skin.[4]

Epidemiology

The incidence of endometriosis in women of childbearing age is around 5 to 15%.[6] The prevalence of cutaneous endometriosis is 0.5 to 1%.[7] The prevalence of primary cutaneous endometriosis is less than 30% in all cases of cutaneous endometriosis. Umbilical endometriosis represents 30 to 40% of the cases of cutaneous endometriosis.[8] Endometriosis in an episiotomy scar occurs in 0.00007% of births; however, this incidence is thought to be underestimated.[9]

Pathophysiology

The theories that provide a basis for the pathophysiology of primary cutaneous endometriosis may be explained by the theory of cellular metaplasia, vascular and lymphatic migration. Meyer, in 1903, proposed the theory of tissue differentiation of the mesothelial cells of the peritoneum into endometrial glands and stroma as a cause of endometriosis. Halban, in 1924. proposed the theory of dispersion of cells of the endometrium from the lymphatic vessels, and similarly, Sampson, in 1925, supported this theory of dispersion of cells through the hematogenous route.[3]

The pathophysiology of secondary cutaneous endometriosis is described on the basis of implantation of the endometrial cells on the cutaneous sites during surgical procedures and those cells behaving as being similar to uterine endometrial cells that undergo proliferation and shedding during the menstrual cycle.[4]

Histopathology

Histopathological examination demonstrates the combination of endometrial glands and stroma in a biopsy specimen obtained from the lesions.

History and Physical

Females within the reproductive age group are usually affected. However, adolescents are also known to be affected. The patient may have a history of prior surgical procedures such as cesarean section, laparoscopy, tubal ligation, hysterectomy, hysterotomy, or episiotomy that might have predisposed the implantation of the endometrial tissue into the scar. The patient usually presents with cyclic pain during menstruation, swelling that may increase at the time of menstruation, a palpable mass, or bleeding from the affected areas in the skin.

The classic presentation of cutaneous endometriosis is a firm papule or nodule which averages a size of 2 cm in diameter. Umbilical endometriosis is to be suspected if a patient arrives with a nodule at the umbilicus with symptoms such as pain, itching, bleeding, or discharge. There may be local signs of inflammation, such as erythema, in the affected areas.[4]

Any similar signs and symptoms, particularly at the scar sites and extremities, should arise suspicion in favor of cutaneous endometriosis. The average time interval between the history of surgical procedures and the onset of symptoms in cases of endometriosis in the gynecological scar is 4.2 years.[9]

Evaluation

Evaluation of cutaneous endometriosis begins with clinical suspicion, which aids in diagnosis. However, the confirmation of the diagnosis can be done by biopsy of the lesion, followed by histopathological examination. History of any surgical procedures done prior is particularly helpful in classifying the disease into primary or secondary lesions.

The use of fine-needle aspiration (FNA) in the diagnosis of scar endometriosis is controversial as this may cause the seeding of the endometriotic tissue in new areas, further aggravating the condition.[9] Therefore surgical excision, when done with a safety margin that is at least 1 cm away from the solid lesion, will serve as both a diagnostic and therapeutic option in cases of scar endometriosis.[6]

Imaging studies such as computed tomography (CT) scan and magnetic resonance imaging (MRI) should be done and are helpful if there is suspicion of cutaneous metastases of a tumor, as in a gastrointestinal malignancy presenting as Sister Mary Joseph’s nodule, which is a differential diagnosis of umbilical endometrioma.

Some patients may undergo a secondary evaluation with biopsy whereby patients were treated with intralesional corticosteroids with no response, initially thinking that the cutaneous lesion was a keloid.[4]

Patients diagnosed with cutaneous endometriosis may need a gynecological workup to evaluate for pelvic endometriosis, as studies in patients with endometriosis in gynecological scars have found that 14% of the total patients have associated pelvic endometriosis.[9]

Treatment / Management

The treatment approach for cutaneous endometriosis can be hormonal or surgical management. Pain management is another aspect, and nonsteroidal anti-inflammatory drugs (NSAIDs) can be used. Hormonal treatment includes the use of gonadotropin-releasing hormonal agonists, danazol, and oral contraceptives. The main mechanism of the hormonal agent is to decrease the cyclical proliferation of the endometrial tissue.

Hormonal treatment is usually meant for reducing the size of the lesions and also provides symptomatic relief for patients before undergoing surgery. Before starting hormonal treatment, patients have to be counseled regarding the side effects, such as amenorrhea, with the use of danazol and leuprolide. In addition, the symptoms of the disease may return once the hormonal treatment is stopped. Danazol use is associated with side effects such as acne, weight gain, hirsutism, and deepening of the voice. Hormonal treatment serves as an alternative treatment for those who do not opt for surgical treatment and also for those with coexistent pelvic endometriosis. However, surgical excision of the lesion with a wide margin is the treatment of the choice.

The recurrence rate is very rare with complete surgical excision. Recurrence is seen if there is an incomplete excision. Regarding the perioperative management of the lesions, the recommendation varies on either performing the surgery at the end of the menstrual cycle, whereby the lesions are smaller in size, or initiating preoperative hormonal agents to reduce the size. Postoperative use of hormonal agents can also be done, and the goal is to prevent a recurrence.[4][5][8] The combination of hormonal treatment followed by surgical excision is a better approach for many cases.(B3)

Differential Diagnosis

A strong suspicion is needed for diagnosis of cutaneous endometriosis since this condition might be mistaken for diseases such as keloid, dermatofibroma, dermatofibrosarcoma protuberans, cutaneous metastasis of cancer (e.g., Sister Mary Joseph nodule), or melanoma. The main feature to keep in mind while suspecting cutaneous endometriosis is that the symptoms it produces are of cyclical nature that may range from cyclical pain only to cyclical increase and decrease in the size of the mass relating to the start and end of the menstruation cycle.

Prognosis

The prognosis of cutaneous endometriosis is considered favorable. If the patient has undergone surgical excision of the lesion, the recurrence rate is low. In a study conducted by Lopez-Soto et al. (2018), out of 33 women who underwent treatment for cutaneous endometriosis, only three had a recurrence (9%).[10]

Complications

Although endometriosis is considered to be a benign condition, malignant transformation has been reported. However, the exact figure of malignant transformation of endometriosis is unknown.  Furthermore, the causes of the malignant transformation of endometriosis are not clear, but genetic, immunologic, and hormonal factors have been implicated.[11][12] One of the complications to be mentioned relating to cesarean scar endometriosis is the ability of the lesion to undergo malignant transformation (typically with an endometrioid or clear cell carcinoma histology), which have more aggressive behavior. Recurrences after the treatment can also be one of the complications.[13][14]