Unexpected uterine malignancy following laparoscopic hysterectomy with morcellation

In Denmark, 4500 hysterectomies are performed each year for benign gynecological diseases. The decision making process regarding the route of hysterectomy depends primarily upon the technical possibilities according to the size and volume of the uterus, but also the patient’s preferences. Evidence favors minimally invasive surgery: vaginal hysterectomy (VH) and laparoscopic hysterectomy (LH), leading to faster recovery, fewer complications and shorter hospital stays [1]. For large fibroids, a possible surgical approach is LH with morcellation, a technique where the fibroids are cut into smaller fragments, utilizing an electric surgical device or manual scalpel to facilitate removal though the small incision holes.

Preoperative evaluation for cervical dysplasia and endometrial malignancy is performed according to current guidelines. Endometrial biopsy is recommended for women >45 years with abnormal irregular bleeding and ultrasound is performed routinely. However, we have no reliable diagnostic tests to identify the rare leiomyosarcoma (LMS). The true prevalence is not known, but the incidence rate is estimated to be 0.4 per 100 000 in the Scandinavian countries [2]. A US database identifying 232 882 women who underwent minimally invasive hysterectomy from 2006 to 2012 in the southern US suggests a prevalence of uterine cancers of 27 per 10 000 morcellations, among the 16% who underwent this operation method [3]. The fragmentation may cause dissemination of occult malignant tissue in the abdomen and peritoneal cavity leading to increased mortality and a shorter progression-free survival for patients with LMS. Yet, valid data demonstrating this association is currently insufficient [4,5]. In the following, four cases of mechanical morcellation of occult LMSs are presented. These patients were all diagnosed in 2012–2013.

Cases

I. A 53-year-old healthy woman had LH with morcellation. Indication: Fibroids. Histology: LMS. Postoperative positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI) scans three months afterwards revealed metastases in the os pubis and pelvis. The patient received chemotherapy and radiation therapy for disseminated disease. Later on, progression and metastatic spread to the lungs and bones (spine, symphysis pubis, calvarial and orbital) occurred. The patient went into terminal phase after fifth line of chemotherapy and received palliative pain treatment until she died, 14 months after being diagnosed.

II. A 54-year-old healthy woman had LH with morcellation. Indication: Fibroids. Histology: LMS. Seven months later PET/CT scan showed FDG PET-negative nodules in the pelvis and the lungs, probably metastases. The patient had chemotherapy for disseminated disease but suffered from chemo-induced cardiotoxicity. Subsequently, progression of the pelvic tumor and lung metastases was treated with reinduction fifth line chemotherapy and radiation therapy, followed closely by an onco-cardiologist. The patient died in hospice care with terminal illness, 33 months after initial diagnosis.

III. A 43-year-old healthy woman had LH with morcellation of a large, cystic degenerate fibroid. Histology: LMS. Postoperative PET/CT scan showed a FDG PET-positive tumor in the pelvic floor. Bilateral salpingo-oophorectomy and omentectomy was performed, but no residual tumor was found. Eight months later the patient had a laparotomy with non-radical excision of recurrence tumor in the pelvic floor (biopsy verified). Following neoadjuvant chemotherapy, radical excision was performed. Neuropathic pain occurred along with recurrence in the pelvic floor and gluteal muscles, tumor embolism, meningeal carcinomatosis and later on lung metastases. The patient received palliative radiation and sixth line chemotherapy and had a ureteral stent bypassing tumor obstruction on the right side. Still alive.

IV. A 48-year-old healthy woman had LH with morcellation. Indication: Fibroids. Histology: LMS. PET/CT scan right after revealed liver and lung metastases plus tumor upon the proximal vagina. Thus, extended disease, which could have been present preoperatively. The patient was treated with first line chemotherapy. Seven months after metastatic disease in the lungs, pelvis, retroperitoneal space progressed and ascites evolved. In the end this patient received treatment consisting of palliative chemotherapy (second line), radiation therapy and ascitic tap, but ultimately died from terminal illness, 10 months after being diagnosed.

Discussion

These cases are all examples of unexpected malignancy discovered after LH with morcellation despite preoperative evaluation according to existing guidelines. For women at risk for uterine sarcoma [age >60 years, black race, prolonged tamoxifen use >5 years, pelvic irradiation, rare hereditary syndromes (renal cell carcinoma, retinoblastoma)] morcellation should be avoided [1]. However, our cases were not informed of the risk for sarcoma, as they had none of these risk factors, so better diagnostic tools are warranted.

Fibroid sizes: 9 cm, 6 cm, 10 cm (doubled in 8 months from 5 to 10 cm) and 13 cm, respectively.

Case	Pt age	Symptoms	Preoperative assessment	Primary surgery	Histologic diagnosis	Disease-free survival	Treatment	Stage	Status
1	53	Metrorrhagia	UL + normal endometrial sampling	LAVH w/morcellation	LMS	3 months	Chemo + radiation	4	Deceased
2	53	NA±	NA±	LAVH w/morcellation	LMS	7 months	Chemo	4	Deceased
3	43	Pelvic pressure Metrorrhagia	UL + normal cervical cytology	LAVH w/morcellation	LMS	8 months	Re-operation +  Chemo + Radiation	4	Alive
4	48	Metrorrhagia	UL + normal endometrial sampling	LAVH w/morcellation. BSO (oophorectomy dxt)	LMS	Extended disease 15 days after surgery (revealed on PET/CT scan)	Chemo + Radiation	4	Deceased

BSO, bilateral salpingo-oophorectomy; LAVH, laparoscopic assisted hysterectomy; LMS, leiomyosarcoma.

±NA, not accessible.

Addressing the risk of malignancy in the informed consent is important. After January 2014, all Danish patients with presumed benign leiomyomas should be informed of the risk of morcellation, a mandatory recommendation from the National Board of Health in 2014. During surgery, alternatives to morcellation should be employed in case of macroscopically suspicious fibroids [5]. Maybe morcellation in the peritoneal cavity is not acceptable at all due to the minimal risk of sarcoma, thus minimal invasive surgeons in Denmark now only use different kinds of coring vaginally or in endobags, also a new recommendation from the National Board of Health in 2015. Not surprisingly, prognoses seem to be less favorable after morcellation than after en bloc removal [5]. Consistent surgical re-exploration and correct staging may optimize the following treatment [6].

US Food and Drug Administration (FDA) has discouraged laparoscopic power morcellation for removal of uterine fibroids, and some power morcellators have been withdrawn. The organization Advancing Minimally Invasive Gynecology Worldwide recommends alternatives to morcellation in postmenopausal women and encourages optimized preoperative evaluation before selecting final surgical procedure. New procedures evolve worldwide as different kinds and sizes of endobags are being produced to ensure safe in-bag-morcellation with no spillage in the peritoneal cavity.