Müllerian‐type carcinosarcoma arising in gastric endometriosis: Case report and review of the literature

The patient was a 49‐year‐old woman with history of pelvic and thoracic endometriosis, which resulted in catamenial pneumothorax. This was initially managed with placement of a right‐sided chest tube, followed by right video‐assisted thoracoscopic surgery due to hemothorax. Due to the severity of her symptoms, the patient underwent total laparoscopic hysterectomy with bilateral salpingo‐oophorectomy (TLH‐BSO) at age 34 with subsequent improvement in endometriosis‐related symptoms. She did not receive hormonal therapy following surgery. Fifteen years later, a 5.1 × 5.1 × 5.4 cm cystic lesion in the proximal stomach was discovered incidentally on CT during a hospitalization for diverticulitis (Figure  1A ). She reported diffuse lower abdominal pain during the admission that resolved with treatment of the diverticulitis, but she remained asymptomatic with respect to the gastric mass. On outpatient follow‐up, abdominal exam was unremarkable. Review of systems was negative for early satiety, dysphagia, nausea, vomiting, and weight loss. Imaging findings, including (A) CT demonstrating cystic lesion emanating from the lesser curvature in the proximal stomach and (B) EUS with submucosal cystic mass measuring 10.3 cm, located 3 cm distal to gastroesophageal junction, with internal solid component; and final pathology, including (C) opened 11.0 × 7.6 × 3.8 cm cystic lesion with nodular excrescences in the gastric body near the lesser curvature, (D) areas of squamous differentiation, (E) chondrosarcomatous component, (F) solid areas composed of poorly differentiated cells, suggestive of a dedifferentiated component with readily identifiable mitotic figures, (G) background of endometriosis, and (H) carcinomatous component with patchy PAX‐8 nuclear staining.

Rayne Peerenboom: Conceptualization; data curation; visualization; writing – original draft; writing – review and editing. Sabrina Wang: Data curation; investigation; visualization; writing – review and editing. Ryan Morgan: Data curation; investigation; supervision; validation; visualization; writing – review and editing. Seth Sankary: Data curation; investigation; supervision; visualization; writing – review and editing. Lindsay Yassan: Data curation; investigation; supervision; visualization; writing – review and editing. Katherine Kurnit: Data curation; investigation; supervision; visualization; writing – review and editing. Mitchell C. Posner: Conceptualization; data curation; investigation; supervision; validation; visualization; writing – review and editing.

EGD/EUS demonstrated a submucosal cystic lesion measuring 10.3 cm (Figure  1B ). Differential diagnosis included congenital cystic lesions such as duplication cyst verses neoplastic lesions such as cystic degeneration of a GIST. 14 Initial biopsies showed invasive poorly differentiated carcinoma with focal squamous differentiation. Full body PET and CT of the chest, abdomen, and pelvis were negative for metastatic disease. Following this workup, the patient underwent exploratory laparotomy and subtotal gastrectomy with end‐to‐side retrocolic Roux‐en‐Y gastrojejunostomy, which was uncomplicated. Final pathology demonstrated a Müllerian carcinosarcoma composed of a range of epithelioid components and a chondrosarcomatous mesenchymal component. The carcinomatous component showed endometrioid differentiation, which was highlighted by PAX‐8 and estrogen receptor immunohistochemical stains, consistent with Müllerian origin. Areas of squamous differentiation and poorly differentiated areas, suggestive of a dedifferentiated component, were also present. The carcinosarcoma was seen in close association with a background of typical and atypical endometriosis (Figure  1C–H ). Resection margins were negative, and 13 lymph nodes were negative for malignancy. CA‐125 was within normal limits at six‐week follow‐up, and MRI pelvis was non‐concerning for residual disease. Postoperative PET CT was also negative. Adjuvant chemotherapy (carboplatin and paclitaxel) was recommended; however, the patient opted for close clinical surveillance with symptom assessment, clinical and pelvic exams, and monitoring of CA‐125 every 3 months.

Four months postoperatively, the patient presented with abdominal pain. A CT of the abdomen and pelvis demonstrated peritoneal implants and ascites, as well as subtle sclerotic lesions. A paracentesis was performed, and cytology was consistent with metastatic adenocarcinoma. A nuclear medicine bone scan demonstrated diffuse osseous metastatic disease. The patient was recommended for systemic chemotherapy. She initiated treatment and is currently receiving carboplatin and paclitaxel.

To our knowledge, this is the first report of EAM in the stomach. To date, there have been six reports of gastric endometriosis in English (Table  1 ), one in Russian, and one in Spanish. 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 EAITs have been reported at other sites in the gastrointestinal tract, most commonly the rectum and sigmoid colon, and other upper abdominal organs including the liver. 15 , 16 Similar to EAOC, endometrioid and clear cell histologies are the predominant subtypes. 1 However, in extra‐ovarian EAM, including EAITs, more reports of endometrial stromal sarcomas, or adenosarcomas are seen in the literature. 1 , 16 , 17 Carcinosarcoma is less commonly reported. Despite its mesenchymal component, carcinosarcomas are now understood to arise from an epithelial precursor, such as endometrioid or clear cell tumors, and are considered to be epithelial tumors. The mechanism of spread of endometriosis beyond the uterus is unknown, although several theories exist to explain the pathogenesis. 18 Initiating events may include metastatic spread via retrograde menstruation, vascular or lymphatic spread, or iatrogenic implantation; metaplasia of specialized cells in the mesothelial lining; persistence and growth of residual Wolffian or Müllerian duct cells; or transformation of resident undifferentiated cells. Several predisposing and propagating factors, including oxidative stress, immune dysfunction, genetic factors, and hormonal changes, may also play a role. 18 The rarity of extrapelvic EAM/EAIT leads to challenges in diagnosis and management. In the present case, the initial imaging findings of a submucosal, cystic lesion favored a duplication cyst, or gastrointestinal stromal tumor. Notably, the majority of previously reported cases of endometriosis in visceral abdominal organs similarly appeared as cystic lesions on CT, 11 and prior cases of gastric endometriosis most often appeared as submucosal lesions on gastrointestinal studies (Table  1 ). However, pathognomonic imaging findings have not been described for EAM; thus, microscopic examination combined with immunohistochemistry is required for diagnosis. In the present case, initial biopsy results demonstrated poorly differentiated carcinoma with focal squamous differentiation but did not reveal the chondrosarcomatous or endometrioid components of the tumor. This highlights the importance of comprehensive pathologic examination and sampling of various tumor components for definitive diagnosis of EAM. Currently, there are no definitive guidelines for the management of EAIT or EAM. Median 5‐year survival for EAM arising in all sites has been estimated at 80%. 19 EAOC, which constitutes the majority of EAM, is generally treated similarly to other forms of ovarian cancer, including use of platinum‐taxane combinations as adjuvant therapy. 20 One review of EAIT found that adjuvant treatment (chemotherapy and/or radiotherapy) was administered for only 10 of 29 patients. 15 EAM arising in the liver has similarly been managed with either adjuvant chemotherapy or clinical surveillance. 13 , 21 In the present case, adjuvant chemotherapy was recommended; however, the patient initially opted for clinical surveillance. Unfortunately, disease recurrence (peritoneal carcinomatosis and diffuse osseous metastatic disease) was confirmed 4 months postoperatively, and the patient initiated treatment with carboplatin and paclitaxel. Our case demonstrates that, although rare, EAM may be considered on the differential for a submucosal gastric lesion. Adequate tissue sampling is required for definitive diagnosis. Close collaboration in an interdisciplinary team including radiology, gastroenterology, pathology, surgical oncology, and gynecologic oncology is necessary for both accurate diagnosis and optimal management.

Written consent was obtained from the patient.

Endometriosis is a common condition, affecting approximately 10% of women of reproductive age. However, both extrapelvic endometriosis and malignant transformation are rare. 1 When intestinal endometriosis does occur, it most commonly involves the sigmoid colon and rectum. 2 To date, there have been eight case reports of gastric endometriosis (Table  1 ). 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 Endometriosis may also involve various other abdominal and extra‐abdominal sites, including the urinary tract, abdominal wall, liver, kidney, pancreas, biliary system, thorax, and central nervous system. 11 Clinical, imaging, pathology, and treatment details of reported cases of gastric endometriosis. CEA & CA 19–9 WNL pre‐op Abbreviations: Abd, abdominal; CA 19–9, carbohydrate antigen 19–9; CA 125, cancer antigen 125; CEA , carcinoembryonic antigen; CT, computed tomography. DCBE, double contrast barium enema; EGD, esophagogastroduodenoscopy; EUS, endoscopic ultrasound; FNA, fine needle aspiration; GEJ, gastroesophageal junction; GI, gastrointestinal; NR, not reported; Para, paracentesis; RUQ, right upper quadrant; WNL, within normal limits. Prior symptoms or diagnosis of endometriosis. Although both pelvic and extrapelvic endometriosis are benign conditions, malignant transformation can occur. The overall risk of malignant transformation has been estimated at 1% for premenopausal females and 1%–2.5% for postmenopausal females. 1 Endometriosis‐associated ovarian cancer (EAOC) constitutes the majority (76%) of these cases. 1 However, endometriosis‐associated intestinal tumors (EAIT) have also been reported, exclusively in the small and large bowel, as has EAM arising in the liver. 12 , 13 To date, there have been no reports of EAM occurring in the stomach. We describe a patient with Müllerian‐type carcinosarcoma arising in gastric endometriosis.

The authors have no conflicts of interests to disclose.