Serous adenocarcinoma arising from endometriosis in cesarean section abdominal wall scar: a case report and literature review

Abstract

Background: Abdominal wall endometriosis has been well-described and can occur after caesarean section. However, malignant transformation of abdominal wall endometriosis is rare, less than 40 cases have been reported so far and its pathogenesis is still poorly understood. Case report: Here, we report a 48-year-old woman, gravida 1, para 1, with a history of uneventful caesarean delivery presented with increasing pain and a rapid growing mass in her cesarean section scar. Serum tumor markers, especially CA125 and CA199 increased remarkably. Physical examination and pelvic magnetic resonance imaging showed a mass sized 15 cm in maximum diameter and the enlarged pelvic lymph nodes. Neoadjuvant chemotherapy and surgery were performed, followed by chemotherapy. The surgery contained radical resection, excision of bilateral accessory, hysterectomy, omentectomy, lymph node excision and abdominal dermoplasty. Histopathological examination showed a serous adenocarcinoma of endometrial origin with lymph node metastasis. Recurrence was noted 3 months after surgery and the patient was followed up until now. 33 literatures on similar cases were reviewed. Conclusion: Extensive lymph nodes metastasis might predict a poor prognosis in case of malignant transformation of abdominal wall endometriosis. Radical resection followed by chemotherapy is the most common treatment. Once recurrence occurs, treatments including chemotherapy and radiotherapy are usually ineffective.

Introduction

Endometriosis is a common gynecological disease and affects 8.5% of women in childbearing age. The most common site of endometriosis is tissues and organs in the pelvic cavity such as bilateral ovaries, uterosacral ligament, fallopian tubes and pelvic wall. However, endometriosis can also occur in other organs and tissues such as bladder, rectum and abdominal wall. In the abdominal wall, it can occur after hysterectomies, particularly after cesarean section [1]. As the prevalence of cesarean sections increases, the incidence of abdominal endometriosis is increasing in recent years, but the malignant transformation of abdominal wall endometriosis is still rare. Here, we report a case of serous adenocarcinoma arising from endometriosis in the cesarean section abdominal wall scar and relevant literatures were reviewed about this rare disease.

Case presentation

A 48-year-old patient received cesarean section 15 years ago (2001), but a mass was found in the cesarean section scar accompanied by cyclic pain in 2002. Subsequently, the mass was excised and pathological examination showed an abdominal scar endometriosis. The margin was free and no further treatment was prescribed after surgery. However, a similar mass was found in the scar again in 2007. Macroscopically, the mass was 2 cm in maximum diameter. Within nearly a year, she felt the mass grew quickly, and the cyclic pain even affected her sleep significantly in menstrual cycle. The recent physical examination in Feb 2016 revealed a mass sized 15 cm in maximal diameter on the middle of the cesarean section scar. The pelvic magnetic resonance imaging (MRI) showed a mass along the abdominal scar and the inguinal lymph nodes were enlarged (Figure 1). Pelvic CT and ultrasonography also revealed a lesion measuring 15 cm×12 cm in the abdominal wall. She received fine needle aspiration biopsy and subsequent pathological examination of the mass and enlarged left inguinal lymph nodes revealed serous adenocarcinoma (Figure 2). Laboratory examination revealed significant increase in the serum tumor markers, especially CA125 (715.6 U/ml) and CA199 (486.3 U/ml). Multi-disciplinary team (MDT) consultation was hold in March 2016 and experts from the departments of oncology, radiotherapy, pathology, imaging, nuclear, surgery, orthopedics and plastic surgery discussed the diagnosis and treatment for this disease. Experts recommended the neoadjuvant chemotherapy to reduce the mass size for further surgical intervention. Three courses of chemotherapy were performed in 4^th March, 24^th March and 14^th April, respectively, with albumin paclitaxel (400 mg on Day 1) and carboplatin (600 mg on Day 2). After chemotherapy, CA125 and CA199 decreased to 20.77 U/ml and 34.75 U/ml, respectively. MRI showed the mass reduced to 7 cm in diameter (Figure 3).

Figure 1.

Pelvic MRI before neoadjuvant chemotherapy in Feb.2016. (A-D) Transverse T2-weighted spectral attenuated inversion recovery (A), diffusion weighted imaging; b=1000 (B), fat-suppressed T1-weighted (C) and gadolinium-enhanced fat-suppressed T1-weighted (D). MR images show an anterior abdominal wall mass (white arrow) and several metastatic lymph nodes (black arrow). The mass is 11.5 cm×7.0 cm×7.9 cm. Mixed signals are found in both T1W and T2W (white arrows in A, C), and hyperintense signal in DWI (white arrow in B). Visible marginal separation enhancement is observed (white arrow in D), which is better shown on T1-weighted image.

Figure 2.

A. Pathological findings of serous adenocarcinoma within the lymph nodes (green arrow) (hematoxylin and eosin stain, magnification ×200). B. High Ki67 & p53 expression shown in the immunohistochemistry (green arrow) (magnification ×200) (left: lymph node; right: Ki67 positive cells). C. Positive p16 expression shown in the immunohistochemistry (magnification ×200). D. Positive WT1 expression shown in the immunohistochemistry (magnification ×200). E. Positive CK7 expression shown in the immunohistochemistry (magnification ×200). F. Negative PR expression shown in the immunohistochemistry (magnification ×200). G. Positive CA125 expression shown in the immunohistochemistry (magnification ×200). H. Positive p53 expression shown in the immunohistochemistry (magnification ×200).

Figure 3.

Pelvic MRI after neoadjuvant chemotherapy in Apr. 2016. (A-D) Transverse T2-weighted spectral attenuated inversion recovery (A), diffusion weighted imaging; b=1000 (B), fat-suppressed T1-weighted (C) and gadolinium-enhanced fat-suppressed T1-weighted (D). MR images show an anterior abdominal wall mass as lesion after chemotherapy (white arrow). The mass is 6.8 cm×2.3 cm×2.9 cm. Hyperintense signal is found in both T1W and T2W (white arrows in A, C), and hyperintense signal in DWI (white arrow in B). Visible marginal separation enhancement is observed (white arrow in D), which is better shown on T1-weighted image. The mass size significantly reduces as compared to that before treatment (Feb. 2016).

The patient received surgery on 17^th May. During laparoscopy, a mass was found to invade the full thickness abdominal wall to the peritoneum. Intra-operative pathological examination was done and malignancy was confirmed. Therefore, she underwent radical resection including: resection of the mass, excision of bilateral accessory, hysterectomy, omentectomy, lymph node excision and abdominal dermoplasty (the mass was so large that the skin was difficult to heal after when it was removed). Macroscopical observation also showed the inguinal lymph nodes, pelvic lymph nodes and para-aortic lymph nodes were all enlarged.

After surgery, pathological examination showed adenocarcinoma and tumor interstitial fibrosis. Immunohistochemistry showed the cancer was ER(-), PR(-), Vim(-), CK7(+), CA125(+), p16(+), p53(+), NapsinA(-), WT1(+), Ki67(70%+) (Figure 2). Post-operative pathological examination revealed an abdominal wall adenocarcinoma without evident evidence of malignancy in the ovaries, fallopian tubes and uterus. Thus, the conclusion was malignant transformation from the abdominal wall endometriosis. There were 11/18 positive pelvic lymph nodes, 1/9 positive para-aortic lymph nodes and 2/5 positive bilateral inguinal lymph nodes. Therefore, adenocarcinoma mass of the abdominal wall perhaps arising from endometriosis after cesarean section was diagnosed.

On 30^th May, the MDT consultation was hold again and chemotherapy was still recommended after surgery. Therefore, three courses of chemotherapy were done on 8^th June, 28^th June and 22^nd July, respectively, with albumin paclitaxel (400 mg on Day 1) and carboplatin (550 mg on Day 2). During the chemotherapy, the serum CA125 and CA199 were normal.

Unfortunately, in the sixth course of chemotherapy, a nodular lesion was found in her abdominal again (Figure 4). On 22^nd August, she was hospitalized for resection of the recurrent mass. Pathological examination of the recurrent tumor revealed adenocarcinoma. Considering platinum resistance, gemcitabine was used for chemotherapy. However, clinically significant myelosuppression occurred after the first course of gemcitabine treatment. Finally, liposomal doxorubicin, ifosfamide and bevacizumab were used for another 3 courses of chemotherapy up to now (Nov. 2016). In addition, Traditional Chinese herbal medication was also used during the treatment and she was followed up by clinical examination, detection of serum tumor markers (CA125 and CA199), and radiological examinations once monthly.

Figure 4.

Plevic MRI of relapse in Aug. 2016. (A-D) Transverse T2-weighted spectral attenuated inversion recovery (A), diffusion weighted imaging; b=1000 (B), fat-suppressed T1-weighted (C) and gadolinium-enhanced fat-suppressed T1-weighted (D). MR images show two abnormal signals in lateral rectus abdominis (white arrow and black arrow). The masses are 1.7 cm×1.4 cm and 1.7 cm×1.0 cm, respectively. Hypointense signal is found in T1W (white and black arrows in C), and hyperintense in T2W (white and black arrows in A) as well as in DWI (white and black arrows in B). Visible marginal separation enhancement is observed (white arrow in D), which is better shown on T1-weighted image.

Discussion

Surgical scar endometriosis is rare with its incidence of roughly 0.03-1% [2] and the risk of transformation of endometriosis to a malignant disease ranges from 0.3 to 1.0% [3]. The malignant transformation of abdominal wall endometriosis is more rare, and less than 40 cases have been reported in the literatures (Table 1). Sampson proposed following 3 criteria for the diagnosis of a malignant transformation of endometriosis: presence of both neoplastic and benign endometrial tissues in the tumor, endometrial histology, and no other additional tumors [4]. Scott added a fourth criterion to these criteria: transition between benign endometriosis and carcinoma [5]. However, only a few cases of malignant abdominal wall endometriosis meet all four criteria.

Table 1.

Literatures of the malignant transformation of abdominal wall endometriosis

Year	References	Nationality	Age (years)	Previous Surgery	Delay (years)	Histology	LN	Surgical Treatment	CT	RT	Follow up (Month)	Outcome
1986	Schnieber, D. and D. Wagner-Kolb [12]	Germany	40	CS	15	CCC	-	LR+TAH+BSO	-	+	18	DOD
1990	Hlitti et al [17]	USA	46	CS	14	CCC	-	LR+TAH+BSO	-	-	30	NED
1996	Markopoulos et al [18]	Greece	40	CS	25	EC	-	LR	-	-	24	NED
1997	Gücer et al [9]	Austria	45	CS	8	EC	-	LR	Carboplatin and cyclophosphamide	-	20	DOD
1998	Miller et al [19]	Canada	38	CS	9	CCC	-	LR+TAH+BSO	Cisplatin	-	60	NED
1999	Park et al [20]	Korea	54	CS	26	CCC	-	LR	-	-	NA	NA
2003	Li et al [21]	China	38	CS	15	CCC	-	LR+TAH+BSO+OMT	Epirubicin, cyclophosphamide and cisplatin	-	14	NED
2003	Matter et al [3]	Switzerland	60	CS	41	EC	-	LR	-	-	18	NED
2003	Ishida et al [1]	Japan	56	CS	24	CCC	-	LR	+	+	48	DOD
2006	Sergent et al [13]	France	45	CS	28	CCC	-	LR+BSO	Taxol and carboplatin	-	6	DOD
2006	Leng et al [10]	China	41	CS	16	Carcinosarcoma	-	LR	Cisplatin and ifosfamide	-	15	DOD
2006	Alberto et al [22]	Irland	38	CS	11	CCC	-	LR	Taxol and carboplatin.	+	NA	NA
2007	Harry et al [23]	UK	55	Open tubal sterilization	30	CCC	-	LR	-	+	18	NED
2008	Bats et al [14]	France	38	CS	13	CCC	+	LR+TAH+BSO+OMT	Taxol and carboplatin.	-	8	REC
2009	William et al [2]	Canada	53	CS	17	CCC	+	LR+TAH+BSO+OMT	Taxol and carboplatin.	-	11	DOD
2009	Matsuo et al [15]	USA	37	LC	10	CCC	+	LR+TAH+BSO+OMT	Taxol and carboplatin.	-	18	REC
2010	Omranipour and Naja [24]	Iran	59	Laparotomy for uterine perforation	20	SC	-	LR+TAH+BSO	Platinum-based	+	12	NED
2010	Bourdel et al [7]	France	43	CS	20	CCC	+	LR+TAH+BSO	Taxol and carboplatin.	+	22	DOD
2010	Drukala et al [8]	Poland	43	CS	17	EC	+	LR+TAH+BSO	9 PAC (cyclophosphamide, cisplatin, doxorubicin) +1 VFP (cisplatin, etoposide, 5-fluorouracil)	+	132	DOD
2011	Da Ines et al [25]	France	48	CS	16	EC+SC	+	LR+LH+BSO	Taxol and carboplatin.	-	15	NED
2011	Yan et al [26]	China	41	CS	NA	CCC	-	LR	+	-	24	NED
2012	Mert et al [27]	USA	42	CS	NA	CCC	-	LR+TAH+BSO+OMT	Taxol and carboplatin.	-	26	NED
2012	Mert et al [27]	USA	51	CS	NA	CCC	-	LR+BSO+OMT	-	+	49	NED
2012	Shalin et al [28]	USA	47	CS	NA	CCC	+	LR	Cisplatin-based	+	7	NED
2012	Li et al [29]	China	49	CS	25	CCC	-	LR	Taxol and carboplatin.	-	8	NED
2013	Fargas et al [30]	Spain	49	CS	15	SC	+	LR+LH+BSO	Taxol and carboplatin.	-	48	NED
2013	Vinchant et al [31]	France	43	CS	10	EC	+	LR	Caelyx and carboplatin	-	N/A	NA
2013	Taburiaux et al [32]	Switzerland	56	CS	29	EC	-	LR	Taxol and carboplatin.	-	17	NED
2013	Stevens et al [33]	USA	51	CS	NA	EC	-	LR	+	+	6	NED
2014	Liu et al [11]	China	39	CS	10	CCC	+	LR+TAH+BSO+OMT	Taxol and carboplatin.	-	12	DOD
2014	Ljichi et al [6]	Japan	60	CS	35	CCC	-	LR	-	-	8	REC
2015	Ruzi et al [16]	USA	41	CS	20	CCC	-	LR+TAH+BSO+OMT	Taxol and carboplatin.	+	6	REC
2015	Ruzi et al [16]	USA	57	CS	30	CCC	+	LR+TAH+BSO	Taxol and carboplatin.	+	NA	NA
2016	This case	China	48	CS	15	SC	+	LR+TAH+BSO+OMT	Taxol and carboplatin; Gemcitabine; Liposomal doxorubicin, ifosfamide and bevacizumab	-	Follow-up	Follow-up

Notes: LN: lumph node invasion, CT: chemotherapy, RT: radiotherapy, BSO: bilateral salpingo-oophorectomy, TAH: total abdominal hysterectomy, OMT: omentectomy, LR: local resection, CCC: clear cell adenocarcinoma, SC: serous adenocarcinoma, EC: endometrioid adenocarcinoma, CS: cesarean section, LC: laparoscopic cystectomy, DOD: died of disease, NED: no evidence of disease, REC: recurrence, NA: not available.

Abdominal wall endometriosis presents as a mass in the abdominal wall, and the patient usually has a history of surgery, most of which is cesarean section. In 33 cases found in the literatures, 30 (91%) had a history of cesarean. Most of carcinomas derived from endometriosis are endometrioid and clear cell adenocarcinoma, accounting for 91% of all the subtypes in 33 cases found in the literature. In our case, a serous adenocarcinoma arose from an endometriotic cesarean scar and was about 15 cm×12 cm accompanied by lymph node metastasis, but primary ovarian mass was not found. Thus, it was a unique case. In this case, immunohistochemistry showed the tumor was positive for CK7, CA125, p16, p53 and WT1(+), but negative for ER, PR, Vim, and NapsinA(-). Additionally, 70% of cells were positive for Ki67 in this case, which is accordance with the diagnostic criteria for serous adenocarcinoma. The diagnosis of malignant transformation of abdominal wall endometriosis should be based on following examinations: 1. reviewing of medical history: patients usually have a surgical history, most of which is cesarean section. 2. imaging examination (such as ultrasonography, CT and MRI) is needed. 3. cytological examination: fine-needle aspiration of the mass may be considered. 4. Detection of serum tumor markers such as CA125.

In the differential diagnosis of abdominal wall mass, following diseases should be considered: abscess, hernia, lymphoma, lipoma, subcutaneous cyst, and hematoma. CA125 has been reported as normal to mildly elevated [6] and has high sensitivity and specificity at 87 and 92%, respectively. In our case, the serum CA125 and CA199 increased, and thus both were used in the follow up.

In 33 cases found in the literatures, surgical treatment was performed for malignant transformation of abdominal wall endometriosis, of which local resection was employed in all cases, and total abdominal hysterectomy or salpingo-oophorectomy in 18 cases (54.5%). However, in all the cases reviewed, malignant transformation was not found in either the uterus or the adnexa. Thus, the significance of hysterectomy and oophorectomy remains unknown.

In our case, the mass was too large to remove, and thus neoadjuvant chemotherapy was performed before surgery. Three courses of neoadjuvant chemotherapy were done and blood biochemical examinations showed both CA125 and CA199 decreased substantially. MRI showed the mass reduced to 7 cm in diameter. The patient received surgical intervention thereafter, including resection of the mass, excision of bilateral accessory, hysterectomy, omentectomy, lymph node excision and abdominal dermoplasty. Since the lymph nodes were positive, chemotherapy continued after surgery with paclitaxel and carboplatin. However, this patient experienced a relapse in the cesarean section scar after three courses of chemotherapy. In the available cases, 9 patients (27.3%) died of this disease [1,2,7-13] and 4 patients (12.1%) had relapse [6,14-16]. Once recurrence occurred, there is no effective treatment including chemotherapy and radiotherapy [11]. As the prevalence of cesarean section is increasing, the incidence of malignant transformation of abdominal wall endometriosis is expected to increase. More studies are warranted to investigate the optimal treatments for malignant transformation of abdominal wall endometriosis.

Conclusion

We report a 48-year-old woman who was diagnosed with serous adenocarcinoma arising from endometriosis in cesarean section abdominal wall scar. She received neoadjuvant chemotherapy, followed by surgical intervention and post-operative chemotherapy, but recurrence occurs during radiotherapy and chemotherapy. By reviewing literature, extensive lymph nodes metastasis usually predicts a poor prognosis. Once recurrence occurs, there is no effective treatment including chemotherapy and radiotherapy. More studies are needed to investigate the optimal treatment for this disease.

Disclosure of conflict of interest

None.