Cutaneous Endometriosis

Etiology

The underlying causes of endometriosis are complex, and the understanding of all of these potential etiologies continues to evolve. Please see StatPearls' companion resource, "Endometriosis," for further information and endometriosis etiologies and pathophysiology. Consequently, the precise etiology of cutaneous endometriosis remains incompletely understood; however, its pathogenesis is often linked to autoimmune disorders such as systemic lupus erythematosus, Sjögren's syndrome, and ulcerative colitis. This association suggests a potential immune system involvement, with a decline in cell-mediated immunity and increased humoral immune responses.

Several theories have been proposed to explain the development of cutaneous endometriosis, with most authors suggesting that endometrial cells are transplanted or migrated by menstrual blood reflux or during surgical procedures such as cesarean sections or other gynecological operations. Seeding of endometrial cells is an etiologic mechanism that has been particularly evident in scar endometriosis, where all documented cases have had a prior surgical history, supporting the idea that transplanted endometrial cells contribute to cutaneous endometriosis development.[4][8]

Experts have also posited alternative etiologies of cutaneous endometriosis, including inflammatory metaplasia or lymphatic spread of endometrial cells.[9] Primary and secondary cutaneous endometriosis frequently occurs in the umbilical region, which may be due to this area having a predisposition for endometrial tissue implantation.[4] In cases of scar cutaneous endometriosis, the endometrial cells are introduced during surgical procedures, making cesarean delivery scars a frequent site for this condition. These varying hypotheses highlight the complex interplay of immune, hormonal, and mechanical factors that contribute to the manifestation of cutaneous endometriosis.[4]

Epidemiology

The incidence of endometriosis in women of childbearing age is around 5% to 10%; of all endometriosis cases, the incidence of cutaneous endometriosis comprises approximately 0.5% to 1%.[10][2][7] Cutaneous endometriosis predominantly affects women of reproductive age, with an average onset age of approximately 35 years.[4] Cutaneous endometriosis accounts for approximately 0.4% to 4% of extragenital endometriosis cases and 30% to 40% of abdominal wall endometriosis cases, in which endometriotic lesions develop within the dermal or subcutaneous layer of the abdomen wall, occur in the umbilicus.[7][11] Other studies have estimated the incidence of abdominal wall endometriosis occurs spontaneously in 20% of women without an incision, and 57% to 92% of cases are identified in women with cesarean delivery scars.[11] Endometriosis in an episiotomy scar occurs in 0.00007% of women following childbirth; however, this incidence is thought to be underestimated.[12]

Pathophysiology

The theories of cellular metaplasia and vascular and lymphatic migration may explain the underlying pathophysiological mechanism of primary cutaneous endometriosis. 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. Similarly, in 1925, Sampson supported this theory of the dispersion of cells through the hematogenous route.[3][1]

The pathophysiology of secondary cutaneous endometriosis is characterized by the implantation of the endometrial cells on adjacent cutaneous sites during surgical procedures. These seeded endometrial cells behave similarly to uterine endometrial cells that undergo proliferation and shedding during the menstrual cycle.[8]

Histopathology

Histologic examination of cutaneous endometriosis typically reveals intradermal endometrial glands lined by pseudostratified columnar epithelium within a fibrovascular stroma. The presence of extravasated red blood cells often aids in diagnosis. Immunohistochemical staining commonly shows glandular epithelial cells positive for estrogen and progesterone receptors, while stromal cells may express CD10.

Core needle biopsy findings frequently include nonciliated columnar epithelium-lined tubular glands, hemosiderin-laden macrophages, and a fibrotic stroma. The definitive diagnostic method remains the histopathologic examination of excised tissue, which often displays glandular structures surrounded by stromal cells, dense fibrous scarring, and hemosiderin deposits within fibroconnective tissue and subcutaneous layers.[13][9][6][14]

History and Physical

Clinical History

Clinical history associated with cutaneous endometriosis includes a history of prior surgical procedures, eg, cesarean section, laparoscopy, tubal ligation, hysterectomy, hysterotomy, or episiotomy that might have predisposed the implantation of the endometrial tissue into the scar. Patients commonly report dyspareunia, chronic pelvic pain, and infertility.[6]

Clinical studies have demonstrated a strong correlation between prior abdominal surgeries, particularly cesarean sections, and the development of cutaneous endometriosis. In a study of 198 patients with cesarean scar endometriosis, nearly all presented with an abdominal mass, and the majority reported cyclic pain.[11] These authors posited that despite its characteristic presentation, cutaneous endometriosis is frequently overlooked due to its rarity and the hesitancy of patients to report symptoms, leading to diagnostic delays.[11]

A key clinical feature of cutaneous endometriosis is its association with cyclical pain and, in some cases, catamenial bleeding, particularly in abdominal wall endometriosis and cesarean scar endometriosis.[14][11] While some women experience significant pain and discomfort, others may remain asymptomatic, leading to underdiagnosis. The most common symptoms include localized pain, swelling, bruising, and discharge.[9] 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.[12]

Physical Examination Findings

Cutaneous endometriosis occurring at the umbilicus classically presents as a tender, reddish-brown, blue, or violaceous nodule or papule, which may fluctuate in size and symptoms based on hormonal influences, including intermittent umbilical pain and cyclic bleeding from the umbilicus. Local signs of inflammation, such as erythema, in the affected areas may be noted.[8] 

The presence of a painful skin lesion that enlarges and becomes tender during menstruation strongly suggests cutaneous endometriosis, though this cyclical pattern may not be present in every case.[4][6] The condition is often mistaken for other dermatologic or surgical pathologies, including keloids, hernias, pyogenic granulomas, melanocytic nevi, and malignant conditions such as metastatic tumors or nodular melanoma.[4] Consequently, biopsy and histopathological examination remain the gold standard for confirming the diagnosis.[6]

Evaluation

Evaluation of cutaneous endometriosis begins with clinical suspicion, which aids in diagnosis. However, the diagnosis can be confirmed through a biopsy of the lesion, followed by histopathological examination.[13] History of any previous surgical procedures is particularly helpful in classifying the disease into primary or secondary lesions.

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.[8] 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.[12]

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.[12] Therefore, surgical excision, when done with a safety margin at least 1 cm away from the solid lesion, will serve as both a diagnostic and therapeutic option in cases of scar endometriosis.[15]

Imaging studies such as computed tomography (CT) scan and magnetic resonance imaging (MRI) may be considered if cutaneous metastasis of a tumor is suspected, eg, a gastrointestinal malignancy presenting as Sister Mary Joseph’s nodule, which is a differential diagnosis of umbilical endometrioma.[7][11]

Dermoscopy has been gaining recognition as a noninvasive and economical emerging diagnostic tool, which often reveals a homogenously red-pigmented area with small red globular structures corresponding to the endometrial glands.[16] Dermoscopic findings associated with cutaneous endometriosis include erythematous or violaceous polypoid projections, brown pigmentation, and dotted vascular structures. Demonstration of these findings on dermoscopic examination can indicate cutaneous endometriosis, though precise diagnostic criteria have not yet been established.[16] 

Treatment / Management

Surgical Management

Wide-margin excision of cutaneous endometriosis lesions definitively treats the condition.[14] Several case studies have stated that complete removal of the endometriotic nodule is the preferred approach.[4][6][17] Some experts recommend a margin-free excision of 5 to 10 mm to reduce the risk of recurrence.[11] In patients with nonpalpable cutaneous endometriosis lesions, preoperative ultrasound guidance is recommended to localize the mass for optimal surgical outcomes.[11](B3)

When endometriotic lesions invade into aponeurotic layers or exceed 50 mm in size, extensive mobilization and the use of polypropylene mesh may be necessary to ensure successful tension-free closure of the abdominal wall. Postoperative complications, eg, hematoma and seroma, are more common in larger nodules, with those measuring ≥30 mm demonstrating a significantly higher complication rate. Despite the success of surgical excision, recurrence rates range between 12.5% and 28.6%, often due to incomplete removal of fibrotic tissue, which may contain residual endometrial cells.[11](B3)

Hormonal Management

For patients who are not candidates for surgery or prefer a noninvasive approach, hormonal therapy, which helps to decrease the cyclical proliferation of the endometrial tissue, can be considered.[6][11] Hormonal treatment can also be utilized to reduce the size of the lesions and provide symptomatic relief for patients before undergoing surgery.[9] Medical management involves the use of agents that inhibit ovarian function, including gonadotropin-releasing hormone (GnRH) agonists, progestogens, and danazol, sometimes in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) for pain relief.[17][4] While these therapies can alleviate symptoms and reduce lesion size, they do not provide a permanent cure and may require long-term administration.(B3)

Additionally, hormonal therapy has been used postoperatively to lower recurrence risks. Patients undergoing treatment with GnRH agonists should be closely monitored for potential adverse effects, eg, decreased bone density. Combination therapy, which involves initial hormonal treatment followed by surgical excision, has been shown to improve outcomes and reduce recurrence rates. Alternative therapies, including cryoablation and intra-lesion alcohol injections, have shown some efficacy, but surgical excision remains the gold standard for both diagnostic and curative purposes.[17](B3)

Strategies for Recurrence Prevention

The recurrence rate is very low with complete surgical excision. Recurrence is seen if there is an incomplete excision. Regarding the perioperative management of the lesions, the recommendation varies: 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 administered to prevent a recurrence.[8][5][18] The combination of hormonal treatment followed by surgical excision is a better approach for many cases.(B3)

Differential Diagnosis

Clinical suspicion is needed for diagnosis of cutaneous endometriosis since this condition might be mistaken for diseases, including such as keloid, dermatofibroma, dermatofibrosarcoma protuberans, cutaneous metastasis of cancer (eg, Sister Mary Joseph nodule), or melanoma.[7][11] The primary feature to consider in patients suspected to have cutaneous endometriosis is that the clinical manifestations produced are of a 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.

Given the potential overlap with other conditions, clinicians should consider cutaneous endometriosis in the differential diagnosis of unexplained abdominal or umbilical masses, especially when symptoms demonstrate a cyclical pattern.[6][17]

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 3 had a recurrence (9%).[19]

Complications

Although endometriosis is considered to be a benign condition, malignant transformation has been reported. However, the exact figure of the 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.[20][21] 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 has more aggressive behavior. Recurrence after treatment can also be one of the complications.[22][23]