Table 1.
Clinical features of 41 patients with extra-genital mullerian adenosarcoma reported in the English literature and of the index case
| Reference number | Author | Age (years) | Site | Size (cm) | Tumour markers | Signs and Symptoms at presentation | Treatment | Sarcomatous overgrowth | Endometriosis | Hormonal therapy | Follow-up |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 4 | Douglas | 18 gravida | Retroperitoneum | 5 × 4.5 × 4 | NR | Anorexia, suprapubic-low back pain, loss of weight, vaginal bleeding, preterm delivery. 24 weeks |
CHT (MTX) | NR | No | No | DOD 10 weeks later with distant metastasis |
| 5a | Clement | 45 | Right Pelvic peritoneum (pelvic mass that extended into the rectum and the bladder) | 7x7x5 | NR | Right lower leg thrombophlebitis, right paravaginal mass | Surgery (partial tumour resection) + RT | NR | No | No | DOD 9 months later due to pelvic recurrence and visceral metastasis |
| 5b | Clement | 73 | Midline Pelvic peritoneum, displcing the bladder anteriorly | 14 | NR | Large pelvic mass with bilateral hydronephrosis. Inability to void | Surgery (complete tumour resection) | NR | No | No | DOD 2 months later (postoperatively massive gastric bleeding necessitating a subtotal gastrectomy occurred but after that the patient’s conditions deteriorated gradually-autopsy not done-) |
| 5c | Clement | 58 | Left Pelvic peritoneum | 16x15x8 | NR | Large pelvic mass. Urinary urgency, rectal pressure | Surgery (partial tumour resection) | NR | Yes | No | AWD local recurrence 15 months later (RT), lung metastases 45 months later (resected) |
| 6 | Bard | 46 | Right pelvic peritonum (the mass was adherent to the right bladder wall and surrounded the right ureter) | 10 × 8 | NR | Weakness and pelvic pain in the right lower extremity. Urinary incontinency | Biopsy + RT | NR | NR | No | DOD 11 weeks later with distant sepsis and metastasis |
| 7 | Kao | 42 | Left round ligament | 10 | NR | NR | Surgery (partial tumour resection) + CHT (Cyt) + RT | NR | No | No | DOD after 10 months due to the tumor |
| 8 | Russell | 29 | Left Broad ligament | 7x6x5 | N.R. | Lower abdominal pain for 2 months and occasional dyspareunia | Surgery (tumour resection) | NR | No | No | Recurrence after 5 months treated with surgery (hysterectomy, bilateral salpingo-oophorectomy) + RT; Died of melanoma after 9 years. |
| 9 | Kerner | 32 gravida | Broad ligament | 15x10x6 and 10x7x4 | NR | Abdominal pain at 28 weeks | Surgery (tumour resection) | No | No | No | AWD omentum and infundibulopelvic ligament recurrence 22 months later |
| 10 | Vara | 62 | Bladder | – | NR | Haematuria, weight loss, suprapubic pain | Surgery (radical cystectomy + urethrectomy) | NR | Yes | No | FOD 12 months |
| 11 | Roman | 55 | Retroperitoneal | NR | NR | NR | Surgery (tumour resection) + RT | NR | Yes | No | First abdominal recurrence 3 years later (resection by thoracoabdominal approach + MPA), a 5 cm perihepatic recurrence 5 years later was completely resected, second perihepatic recurrence 7 years from original tumour (resection of recurrence and TMX), 6 months later intrahepatic metastasis (CHT for recurrences (cisplatin-ifosfamide, ifosfamide, doxorubicin), later atrial tumour (resection of cardiac tumour and oral therapy with etoposide). Died after 10 years from original tumour and 70 days after resection of cardiac tumour. |
| 12 | De Jonge | 16 | Pelvic peritoneum and infracolic omentum | NR | Ca 125 > 190 U/ml | Severe Abdominal distension and pain | Surgery (tumour resection with extirpation of pelvic mass, left fallopian tube, infracolic omentum and appendix) | Yes | No | NR | Three weeks after primary surgery a pelvic mass recurred (CHT with doxorubicin and ifosfamide), first recurrence of the pouch of Douglas 8 months later (CHT cisplatinum, etoposide and ifosfamide), second recurrence of the pouch of Douglas 14 months later the first recurrence (bilateral salpingo-oophorectomy, abdominal hysterectomy, pelvic and para-aortic lymphadenectomy and hormonal therapy) FOD 57 months after the last cycle of chemotherapy |
| 13 | Benda | 65 | Vaginal apex | 10x7x8 | NR | Pelvic pressure and urinary frequency | Surgery (tumour resection) | NR | No | No | Three years later a 6 cm vaginal recurrence was completely resected; 5 yrs. after first recurrence a 12 cm vaginal recurrence was completely resected and a progesterone therapy was delivered; 7 years after the second recurrence a 17 cm pelvic recurrence was partially resected and a TMX (2 weeks) therapy followed by P (2 weeks) therapy was delivered; 10 months after the third recurrence a fourth pelvic recurrence was partially resected and treated with RT. AWD 16 years |
| 14 | Ostor | 49 | Pouch of Douglas | 19x8x3 | NR | Right Iliac fossa pain | Surgery (tumour resection and abdominal hysterectomy and bilateral salpingo-oophorectomy) Radiotherapy and Hormonal therapy (Medroxyprogesterone) | NR | No | No | AWD recurrence 5 weeks later (chemotherapy cisplatin and ifosfamide). Persistence of some nodularity on the pelvic floor 18 months later |
| 15 | Inoue | 54 | Left paracolpium | 15x11x10 | Ca 125: 860 U/ml | Brownish vaginal discharge Small ulcer in the left posterior fornix |
RT+ Surgery (tumour resection+ total abdominal hysterectomy, bilateral adnexectomy, abdominal perineal resection with colostomy) |
NR | Yes | No | FOD 1 year later |
| 16 | Judson | 42 | Vaginal cuff | 6 × 3 | NR | Endometriosis recurred three times and was treated with surgery, hormonal therapy (megestrol, danazol) and brachytherapy. Lesion coming out from vagina | CHT (paclitaxel and carboplatin followed by TMX) | NR | Yes | No | 12 months later a 4 cm vagina recurrence was excised and a RT was delivered than was FOD |
| 17 | N’Senda | 54 | Liver | 20 × 12 | CA 15–3 and CA 19–9, were three and fourfold normal level respectively | Right-sided epigastric pain | Surgery (tumour resection: A segment -IV enlarged right hepatectomy extended to adjacent diaphragm) | No | Yes | HRT | FOD 24 months |
| 18 | Kato | 20 | Abdominopelvic peritoneum | 23x23x14 | CA 125: 1000 IU/ml | Fatigue and constipation | Surgery (tumour resection) | NR | No | No | FOD 1 years later |
| 19a | Yantiss | 36 | Sigmoid | 10,5 | NR | Hypermenorrhoea, 6 months abdominal pain | Surgery (tumour and sigmoid resection) | NR | Yes | NR | FOD 36 months |
| 19b | Yantiss 2000 | 50 | Colon | NR | NR | NR | Surgery (tumour and colon resection) | NR | Yes | NR | FOD 24 months |
| 19c | Yantiss 2000 | 83 | Small bowel | 15 | NR | Abdominal mass obstruction | Surgery (tumour and bowel resection) | NR | Yes | NR | NR |
| 19d | Yantiss 2000 | 43 | Small bowel | 6.5 | NR | NR | Surgery (incomplete tumour resection) | NR | NR | ER T | NR |
| 20 | Visvalingam | 50 | Abdominopelvic peritoneum | 13 kg | NV | Painless abdominal swelling | Surgery (tumour resection), Hormonal therapy (progesterone) | NR | No | No | Ten months later a 50 cm pelvic recurrence was resected (tumour debulking, extrafascial hysterectomy, omentectomy, appendicectomy). DOD 16 months later (Autopsy revealed tumor nodules throughout the abdominal and pelvic cavity limited to the peritoneal surface) |
| 21 | Anderon | 46 | Vagina | 10 cm | NR | Removal of the vaginal mass, stalk and paravaginal tissue. | No | Yes | Yes | FOD after a parametrium recurrence that was treated with external radiotherapy and interstitial brachytherapy. | |
| 22 | Dincer | 50 | Perisplenic Peritoneum | NR | NR | Large bowel obstruction in a woman with Endometriosis treated with aromatase inhibitor | Surgery (partial tumour resection) + Chemotherapy (anthracycline) + experimental anti-angiogenesis agent | Yes | Yes | No | DOD 13 months later due to no regression of the pelvic tumour |
| 23 | Hines | 43 | Peritoneum (from posterior cul-de-sac through the middle to upper abdomen) | NR | Ca 125: 824 IU/ml | Dysmenorrhea and endometriosis | Surgery (tumour resection) + Hormonal therapy (medroxyprogesterone acetate) | No | Yes | No | FOD 10 months later |
| 24 | Murugasu | 23 | Pouch of Douglas | 11 | Ca 125: 378 IU/ml; CEA: 13. | Right-sided pelvic pain | Surgery (tumour resection), Chemotherapy (Mesna, adriamycin, ifosfamide), Radiotherapy | Yes | Yes | No | FOD 1 years later |
| 25 | Liu | 56 | Vaginal Vault | 16 | NR | Urinary incontinence and prolapse in a woman with Vaginal endometriosis (TAH, BSO). | Surgery (tumour resection with adherent structures including rectum and part of the bladder wall) + Chemotherapy (ifosfamide and cisplatin) + Radiotherapy | No | Yes | ERT | FOD |
| 26 | Raffaelli | 50 | Rectovaginal septum | Not reported | NR | Deep dyspareunia, rectal pain, periovulatory pelvic pain in a woman with diagnosis of endometriosis | Surgery (Hysterectomy, left salpingo oophorectomy and partial vaginectomy) + Hormonal therapy (megestrol acetate) | No | Yes | No | Pelvic recurrence 14 months after first surgery (resection of the mass, chemotherapy with ifosfamide and epirubicin-stopped due to intolerance- and radiotherapy 52,90Gy-stopped due to toxic side effect) FOD 9 months after the last surgery |
| 27 | Toyoshima | 52 | Vaginal cuff | 11 cm | High level of Ca125 | Neoadjuvant therapy and surgical removal of the tumour, the vaginal wall and the greater omentum | Yes | Yes | No | After a month the first lung recurrence treated with chemotherapy, and then a second abdominal recurrence treated with chemotherapy. DOD after 9 months from surgery | |
| 28 | Kanngurn | 48 | Pelvic peritoneum | 26x26x10 cm | NR | Right lower quadrant pain | Surgery (tumour resection, Hysterectomy, bilateral salpingo oophorectomy) + Chemotherapy (Bleomycin, Etoposide and Cisplatinum × 7 cycles). | Yes | No | No | Abdominal recurrence 8 months later during the fourth cycle of therapy (13, 5 × 7, 8 × 13 cm), lost at follow-up. |
| 29 | Chang | 37 | cul-de-sac | 3.5 | NR | Vaginal bleeding in a woman with endometriosis (TAH, BSO and hormonal therapy) | Surgery (resection of cul-de-sac tumour, left anterior proctectomy, coloanal anastomosis) | No | yes | yes | FOD 36 months |
| 30 | Milam | 47 | Right inguinal channel | 12 × 4 | CA 125: 76,8 | Persistent and enlarged groin mass | Surgery (tumour resection) | No | Yes | HRT | FOD 12 months later |
| 31 | Huang | 41 | Mesentery of the terminal ileum, right colon and pelvic sidewall | 10 | NV | Right lower quadrant pain and nausea | Surgery (TAH, bilateral salpingo oophorectomy, omentectomy, resection of cul-de-sac and sigmoid colon nodules, and pelvic and para-aortic lymph node dissection) + Chemotherapy (ifosfamide+ cisplatin) | No | Yes | No | Peritoneal recurrence at 1 month and chemotherapy (liposomal doxorubicin) FOD for 18 months |
| 32 | Han | 34 | Vagina | 7 × 6 | High value | Tumour resection, hysterectomy and bilateral salpingo-oophorectomy | No | Yes | No | The patient had 4 vaginal recurrences. The first was treated with chemotherapy, the second was treated with surgery, the third with surgery and adjuvant therapy and the fourth with chemotherapy. FOD | |
| 33 | Maeda | 47 | Left pelvic side wall | 3 | NR (LDH level 993 IU/ml) | Acute lower abdominal pain due to pedunculated subserosal myoma | Surgery (tumour resection, bilateral salpingo-oophorectomy, total abdominal hysterectomy) | Yes | Yes | TMX | Four weeks later 8 cm recurrent tumour in the right pelvis treated with salvage surgery. One month after second surgery recurrent tumour in pelvis and upper abdomen that was treated with salvage chemotherapy (liposomal doxorubicin), 5 cycles). FOD three months after chemotherapy. |
| 34 | Patrelli | 49 | Pouch of Douglas | 10 × 6 | CA 125 and Ca 19–9 slightly elevated | Pelvic pain | Surgery (tumour resection) | Yes | No | No | Eighteen months later recurrence of posterior vaginal fornix (resected), 6 months after recurrence another posterior vaginal fornix recurrence (radical hysterectomy with bilateral salpingo-oophorectomy, and pelvic lymphadenectomy and Radiotherapy-50Gy-) FOD |
| 35 | Clarke | 50 | Pelvic peritoneum (partially adherent to the posterior uterine serosa) | 34x14x7 | NR | NR | Surgery (omentectomy, appendicectomy, removal of small bowel mesenteric implants) | NR | NR | NR | |
| 36 | Karateke | 26 | Pouch of Douglas | 18 | NR | Lower abdominal distention and left lower quadrant pain | Surgery (tumour resection) | No | Yes | No | FOD 24 months later |
| 37 | Yang | 36 | Rectum | 2,5 × 2 | NR | Loose stool, dysmenorrhea, deep dyspareunia, haematochezia | Surgery (tumour resection) | No | Yes | No | FOD 60 months |
| 38 | Kar | 30 | Omentum | NR | NR | Abdominal distension due to abdominal mass and free fluid | Surgery (hysterectomy, bilateral salpingo oophorectomy, omentectomy) and preoperative chemotherapy | Yes | Yes | No | NR |
| 39 | Pontrelli | 58 | Vagina | 5 cm | NR | Bleeding vaginal lesion | Vaginectomy and parametrectomy using the laparoscopic approach, total colpectomy and partial cystectomy. After that the patient was candidate for progestin therapy. | Yes | Yes | Yes | FOD at November 2016 |
| 40 | Mandato | 79 | Abdominal Peritoneum | 16 × 11 | NV | Abdominal distension | Surgery (tumour resection, bilateral salpingo-oophorectomy, total hysterectomy) Residual absent |
Yes | No | No | 4 weeks later had a pelvic recurrence; DOD 4 months after diagnosis |
Abbreviations: AWD alive with disease, DOD died of disease, NER no evidence of recurrence, UK unknown, NR not reported, NV normal value, FOD free of disease, CHT chemotherapy, MTX methotrexate, RT radiotherapy, Cyt cyclophosphamide, MPA medroxyprogesterone acetate