Radical resection of an endometrioid carcinoma arising from endometriosis in the round ligament within the right canal of Nuck: a case report and literature review.

•A patient had endometrioid adenocarcinoma arising from endometriosis in the canal of Nuck.•The tumor invaded muscles in the inguinal region.•She showed favorable prognosis by radical surgery and adjuvant chemotherapy.

Introduction

Since Sampson (1925) first reported the malignant transformation of ovarian chocolate cysts, there have been many reports on malignant transformation of endometriosis. Most malignant tumors associated with endometriosis occur in the pelvic cavity; however, 2.5–6.0% of these tumors were observed at extrapelvic sites (Irvin et al., 1998). The inguinal region was reported to be associated in 1.8% of cases of malignant transformation of endometriosis (Irvin et al., 1998). Among these cases, only 4 were associated with the canal of Nuck.

The canal of Nuck is an embryological remnant in females, which is analogous to a patent process vaginalis in males. The entire fold is normally obliterated within the first year of life in female infants. Occasionally, the canal of Nuck remains patent and permits the seeding of endometriotic tissue in inguinal soft tissues (Irvin et al., 1998; Ito et al., 2010; Mesko et al., 1988; Sun et al., 1979).

Here, we present a case of an endometrioid carcinoma arising from endometriosis in the round ligament within the canal of Nuck and coexisting with a hydrocele of the canal of Nuck. The patient showed favorable prognosis with radical resection of the tumor and adjuvant chemotherapy.

Case report

A 40-year-old Japanese woman (gravida 2, para 2) was aware of a gradually enlarging nodule on the right side of her pubis for 3 years. She visited a hospital because of pain and bleeding at the nodule, and she was referred to Kumamoto University Hospital for suspicion of malignancy.

She had a regular 28-day menstrual cycle with no history of hormonal therapy and had no particular medical history. With regard to family history, her paternal uncle had gastric cancer and her paternal aunt had lung cancer.

At the initial examination, a 6-cm mass with an irregular surface was observed on the right side of the pubis. No abnormal findings were identified in the pelvic cavity on bimanual examination. The result of Pap smear was negative for intraepithelial lesion or malignancy, and the endometrial cytology was negative for malignancy.

Biopsy of the inguinal mass indicated an adenocarcinoma composed of columnar cells. The tumor cells were immunohistochemically positive for cytokeratin 7, estrogen receptor, and progesterone receptor, and negative for cytokeratin 20 and gross cystic disease fluid protein 15. These findings suggested that the tumor might have originated in tissues associated with the female genital tract. Pelvic magnetic resonance imaging (MRI) identified a 6-cm solid mass with a 3-cm cystic component in the right inguinal region. The MRI scan revealed that the tumor invaded into the right pectineal, rectus abdominis, and oblique abdominal muscles, and had continuity with the round ligament in the right inguinal canal (Fig. 1A–D). No remarkable abnormalities were found in the uterus and the bilateral ovaries. Positron emission tomography/computed tomography indicated metastasis to the right inguinal lymph node, but no distant parenchymal metastasis was observed. The serum CA 125 level was 226.8 U/ml and CA 19–9 level was 67.7 U/ml, whereas the CEA level was within the normal range. Based on these findings, the tumor was suspected to be an adenocarcinoma arising from the right round ligament, possibly associated with endometriosis.

Fig. 1

Contrast-enhanced pelvic magnetic resonance imaging. A 6-cm solid mass (A, B, C, D: white arrow) is seen in the right inguinal region. A cystic component is located at the lateral caudal site of the solid mass (B, C: black arrow), with a thin, regular, smoothly demarcated wall. The solid mass is thought to have continuity with the round ligament (D: arrowhead) in the right inguinal canal. (A: sagittal section, T2-weighted image; B: transverse section, T2-weighted image; C: transverse section, T1-weighted image; D: transverse section, contrast-enhanced T1-weighted image).

En bloc resection of the inguinal tumor and the invaded surrounding tissues was performed through partial radical vulvectomy, clitoridectomy, and resection of the right pectineal muscles, rectus abdominis muscles, oblique abdominal muscles, inguinal ligament, and round ligament. Additionally, the bilateral inguinal lymph nodes were resected en bloc together with exploratory laparotomy. Laparotomy revealed no macroscopic abnormal findings in the uterus, bilateral fallopian tubes, or ovaries. In addition, the lesions of endometriosis were not identified in the pelvic peritoneum. Intraoperative pathological assessment revealed metastasis to the left deep inguinal lymph nodes; therefore, bilateral pelvic lymph node dissection was performed. Finally, reconstruction was performed with a rectus abdominis myocutaneous flap for the right inguinal area and a sartorius muscle flap for the left inguinal area.

The resected specimen showed a 6-cm yellow solid mass where the right round ligament ended. A 3-cm cyst containing white fluid was located at the lateral distal site of the end of the right round ligament. Microscopic examination revealed the inguinal tumor composed of well-differentiated endometrioid carcinoma, associated with endometriosis on the round ligament in the right canal of Nuck (Fig. 2B, C). The cyst wall was covered by atypical columnar cells and did not contain normal epithelium or mesothelium. Well-organized bundles of collagen fibers arranged in a parallel fashion were also observed in the superficial portion of the cyst wall, indicative of its peritoneal-origin. Based on these findings, the tumor was considered to have involved hydrocele of the canal of Nuck (Fig. 2D). Metastatic tumor was identified in the both inguinal and left external iliac lymph nodes. Margins of the surgical specimens were uninvolved by the tumor. Consequently, the diagnosis of endometrioid carcinoma, associated with endometriosis in the right round ligament within the canal of Nuck, was rendered. Adjuvant chemotherapy with paclitaxel (175 mg/m2) and carboplatin (area under the curve, 6) was administered.

Fig. 2

Macroscopic and microscopic findings of the resected inguinal tissue. The tumor was resected en bloc with invaded surrounding tissues (A). Microscopically, a well-differentiated endometrioid carcinoma is observed in continuity with the endometriotic foci in the round ligament within the right canal of Nuck (B, C). The cyst wall is covered with atypical columnar cells and has a bundle of collagen fibers (D: arrowhead). B, C, D: Hematoxylin-eosin staining, scale bars, 200 μm.

Twelve months after the initial surgery, the patient had irregular vaginal bleeding. Cytology of the endometrium revealed suspicious features of malignancy, and the endometrial biopsy showed endometrial intraepithelial neoplasia (EIN). MRI revealed endometrial thickness with clear junctional zone in the uterus and no remarkable changes in the ovaries. At this point of time, considering the history of endometriosis-associated malignancy, we recommended total hysterectomy and resection of both adnexa; however, the patient decided to preserve one ovary. Therefore, we performed abdominal total hysterectomy, left salpingo-oophorectomy, and right salpingectomy. Laparotomy revealed the macroscopic lesions of endometriosis in pelvic peritoneum, which was diagnosed as endometriosis in intraoperative rapid pathological diagnosis. Bilateral ovaries were macroscopically normal without evidence of endometriosis.

She was postoperatively diagnosed with endometrial cancer (stage IA FIGO, well differentiated (Grade1) endometrioid carcinoma), as well as EIN.

Furthermore, after obtaining the patient's consent on additional surgical treatment, we performed right oophorectomy and omentectomy 5 months after the second surgery. The resected ovary was microscopically confirmed to be well differentiated (Grade1) endometrioid carcinoma of stage IA FIGO, associated with endometriosis in the right ovary. She has been followed for 37 months the first surgery without no evidence of recurrent tumor and had no adverse events related to the surgery. To date, we have not gained the patient's consent for some genetic testing.

Discussion

Endometriosis is one of the most common benign gynecologic diseases and is estimated to occur in 10–15% of women of reproductive age (Goldman and Cramer, 1990). Endometriosis is histologically defined as the presence of ectopic endometrial glands and stroma at extrauterine sites. It rarely occurs in the inguinal region, and inguinal endometriosis has been estimated to be found in 0.3–0.6% of all endometriosis patients (Candiani et al., 1991). In endometriosis patients, malignant transformation is thought to occur in approximately 0.7–1.0% of cases (Kobayashi et al., 2007; Matter et al., 2003). The diagnosis of malignancy arising from endometriosis is made according to the criteria proposed by Sampson (1925). In addition to these criteria, Scott (1953) suggested a strict criterion. The present case fulfilled all these criteria; therefore, we made a diagnosis of a well-differentiated endometrioid carcinoma arising from endometriosis in the round ligament within the right canal of Nuck.

The canal of Nuck is a very uncommon site for endometriosis. Partial obliteration of the canal of Nuck by endometriosis sometimes occurs, resulting in the formation of a hydrocele in the canal of Nuck (Anderson et al., 1995; Huang et al., 2003). In this case, endometriosis and malignant transformation were observed at a more proximal site of the canal of Nuck than that of the hydrocele.

A malignant tumor associated with endometriosis in the canal of Nuck is rare, and only 4 cases have been reported in the literature (Table 1). Inguinal malignant tumors associated with endometriosis have been reported to be common on the right side (Bergamini et al., 2014; Candiani et al., 1991). The suspected course of endometriosis formation in the region is migration of endometrial tissue down the round ligament (Clausen and Nielsen, 1987). For accurate prediction of occurrence, 2 theories have been proposed. The first is that the sigmoid colon protects the left inguinal canal and the second is that the right round ligament may be easily exposed to endometrial cells in ascites as intraperitoneal ascites move in a clockwise direction (Candiani et al., 1991; Sun et al., 2010).

Table 1

Malignant tumors arising from endometriosis in the canal of Nuck.

Case	Author, year	Age	Site	Symptoms	Treatment	Histology	Follow-up
1	Sun et al. (1979)	64	Right inguinal legion	Mass	Excision, exploratory laparotomy, re-excision	Primary low grade adenocarcinoma	Local recurrence at 3 years, alive with no evidence of the disease 8 years after first surgery
2	Mesko et al. (1988)	57	Right inguinal legion	Enlargement of a mass	Excision, exploratory laparotomy, re-excision and ILND after 3 months, RT	clear cell adenocarcinoma	Local recurrence at 3 months, alive with lung metastasis at 2 years
3	Irvin et al. (1998)	34	Left inguinal legion	Enlargement of a mass	Excision, wedge resection of the pulmonary nodule after 21 months, right upper lobectomy 9 months after the wedge resection,	Endometrial stromal sarcoma	Lung metastasis at 21 months, focal recurrence in lung at 9 months after the second surgery, alive with no evidence of the disease 6 years after the first surgery
4	Ito et al. (2010)	50	Right inguinal legion	Mass	Excision	Endometrioid adenocarcinoma	Alive with no evidence of the disease at 1 year
5	Our case, 2017	40	Right inguinal legion	Enlargement of a painful mass	Excision, ILND, PLND, reconstruction of inguinal region with the rectus abdominis myocutaneous flap, TAH + LS + RSO, sampling of pelvic nodules, right oophorectomy, OMT	Endometrioid carcinoma	Endometrial cancer was found 12 months after the first surgery, ovarian cancer was also found 3 months after the second surgery, alive with no evidence of disease 20 months after the third surgery

ILND, inguinal lymph node dissection; RT, radiotherapy; PLND, pelvic lymph node dissection: TAH, total abdominal hysterectomy; LS, left salpingectomy; RSO, right salpingo-oophorectomy; OMT, omentectomy.

Although a therapeutic strategy for malignant transformation of endometriosis has not been established, it is believed that primary surgery with complete resection should be performed. Confined to the site of the origin, the prognosis of malignant transformation of extragonadal endometriosis was good with a 5-year survival rate of 100% (Irvin et al., 1998). However, with disseminated intraperitoneal disease, the prognosis was very poor, with a 5-year overall survival rate of 12% (Irvin et al., 1998). Among the 4 previous cases of malignant transformation of endometriosis within the canal of Nuck, all underwent excision of the tumor and no case received adjuvant chemotherapy. Although they showed no invasion to tissues around the canal of Nuck, 2 of the 4 cases (Table 1, case 1, 2) showed recurrence in the inguinal region at 3 months and 3 years after the first surgery, respectively. Additionally, 2 of the 4 cases (Table 1, case 2, 3) showed lung metastasis at 21 months and 2 years after the first surgery, respectively (Irvin et al., 1998; Ito et al., 2010; Mesko et al., 1988; Sun et al., 1979). D.

In the present case, metachronous occurrence of endometriosis-associated malignancy was confirmed pathologically. When endometriosis-associated malignancy is suspected, clinicians should consider the possibility that persisting endometriosis can contribute to the development of additional cancer in the future. On the basis of these considerations, clinicians need to provide precise information of the patient and determine an appropriate treatment strategy.

Here, we reported a rare case of an advanced endometrioid carcinoma arising from endometriosis in the round ligament within the canal of Nuck, along with a hydrocele in the canal of Nuck. Radical resection and adjuvant chemotherapy were effective.

Ethical consent

Consent was obtained from the patient for publication of this case report.

Conflict of interest statement

The authors have no conflicts of interest to declare.