Review Article
Peritoneal Nodules after Laparoscopic Surgery With Uterine Morcellation: Review of a Rare Complication Debra S. Heller, MD*, and Bernadette Cracchiolo, MD, MPH From the Departments of Pathology and Laboratory Medicine (Dr. Heller), and Obstetrics, Gynecology, and Women’s Health (Drs. Heller and Cracchiolo), Rutgers–New Jersey Medical School, Newark, New Jersey (both authors).
ABSTRACT The risk of occult malignancy being present at the time of uterine morcellation has been estimated to be about 1%. Dissemination of both benign and malignant disease may occur after morcellation, leading to a variety of peritoneal nodules. These lesions are reviewed. Journal of Minimally Invasive Gynecology (2014) 21, 384–388 Ó 2014 AAGL. All rights reserved. Keywords:
DISCUSS
Adenomyosis; Endometriosis; Leiomyoma; Leiomyosarcoma; Uterine neoplasms
You can discuss this article with its authors and with other AAGL members at http://www.AAGL.org/jmig-21-4-JMIG-D-13-00604
Use your Smartphone to scan this QR code and connect to the discussion forum for this article now* * Download a free QR Code scanner by searching for ‘‘QR scanner’’ in your smartphone’s app store or app marketplace.
Morcellation of uterine tissue, in the course of hysterectomy or myomectomy, is part of the arsenal of minimally invasive gynecologic procedures. It enables removal of tissue fragments through a smaller abdominal wall incision or a colpotomy incision. Rarely, viable tissue fragments may attach to the peritoneum-lined surfaces in the pelvis and even in the upper abdomen, and nodules may develop. In addition, there may be limitations on the ability to assess criteria for malignancy at pathologic evaluation of the surgical specimen, as well as concern of dissemination of unsuspected malignant disease. On the basis of finding 1 possible epithelioid trophoblastic tumor in 101 morcellated specimens, Hagemann et al [1] estimated the risk of occult malignancy at 1%. Although such cases are uncommon, minimally invasive surgeons should be aware of this potential complication. A systematic review of the literature is presented herein.
The authors declare no conflicts of interest. Corresponding author: Debra S. Heller, MD, Department of Pathology, Rutgers–New Jersey Medical School, UH E158, 185 S Orange Ave, Newark, NJ 07103. E-mail: [email protected] Submitted November 6, 2013. Accepted for publication January 2, 2014. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ - see front matter Ó 2014 AAGL. All rights reserved. http://dx.doi.org/10.1016/j.jmig.2014.01.003
Leiomyomas and Subsequent Parasitic Leiomyomas and Iatrogenic Diffuse Peritoneal Leiomyomatosis Parasitic leiomyoma has traditionally been thought to be secondary to a pedunculated subserosal leiomyoma that lost its blood supply and developed a new one at the parasitic site. More recently, occasional cases have been reported after laparoscopic surgery with morcellation of leiomyomas [2]. In addition to single lesions, diffuse peritoneal leiomyomatosis (DPL) has occurred. Symptoms of DPL include urinary retention [3], dysuria, and pelvic pain [4]. DPL is a rare condition, first described in 1952. In a literature search by Al-Talib and Tulandi [5], 132 cases were found in the English literature, and they attributed 5 of these to an iatrogenic cause after morcellation. Since then, scattered case reports have increased the reported numbers in the literature. Relationship to hormonal stimulation is supported by estrogen and progesterone receptors in the lesions and by the occurrence of cases in an increased hormonal milieu such as pregnancy, oral contraceptive use, hormone replacement therapy, tamoxifen administration, estrogen-secreting tumors, or ovarian stimulation [5]. Takeda et al [6] reported DPL diagnosed 6 years after laparoscopic myomectomy with morcellation. The patient, aged 39 years at the time of her second presentation, was found to have asymptomatic lower abdominal nodules ranging from 1 to 6 cm attached to the peritoneal surfaces including the round ligament, omentum, vesicouterine pouch, Douglas pouch, and pelvic sidewall.
Heller and Cracchiolo.
Peritoneal Nodules after Uterine Morcellation
The uterus demonstrated no important pathologic findings. The nodules were resected during laparoscopy. Histopathologic analysis revealed that the lesions were histologically consistent with leiomyomas. At immunohistochemistry, both the initial and recurrent lesions stained positive for progesterone receptor. Other studies have demonstrated both estrogen and progesterone receptors, which along with the premenopausal stage of most patients suggests a role for hormonal stimulation of disseminated tissue [5] Regression has been reported with administration of gonadotropin-releasing hormone agonist [7] or aromatase inhibitor [8]. Rarely, DPL has undergone malignant transformation [9]. Ordulu et al [10] reported a similar case after laparoscopic supracervical hysterectomy with morcellation of leiomyomas in which the nodules developed 7 years after the initial surgery. The authors demonstrated an association between the chromosomal alterations of both the original leiomyoma tissue and the DPL, with both having a 3q deletion. They also noted the association of DPL in premenopausal women and suggested that the condition is related to estrogen and progesterone stimulation. Cucinella et al [11] reported 4 DPL cases after morcellation of myomas, for a prevalence of 1.2% during their 3-year study. Two of the patients had symptoms, and 2 did not. The authors recommended inspection and irrigation of the abdominopelvic cavity at the end of the surgical procedure. Short-term complications of retained uterine tissue after morcellation have also been reported, including infectious complications with necrosis of the retained tissue, requiring a repeat operation [12]. Of interest, the fastest recurrence, at 24 months, was in a patient with an intervening pregnancy, further supporting hormonal stimulation as contributory. Smooth muscle nodules can manifest many years after morcellation. One of the cases reported by Larraın et al [13] manifested 16 years after initial laparoscopic morcellation. Dissemination of myoma fragments is thought to be the underlying cause of DPL. Epstein et al [14] reviewed the video footage of the original myomectomy in their patient with DPL and noted dispersed pieces of myoma in the pelvis. They advised careful removal of all fragments [14]. In the case reported by Paul et al [3], a 28-year-old woman was found to have multiple parasitic leiomyomas at 2½ years after morcellation. The location of one of the nodules on the parietal peritoneum at the laparoscopy port site lends support to iatrogenic dissemination. Of interest, in the case reported by LaCoursiere et al [4], cervical tissue also identified with smooth muscle fragments favors including implantation as the mechanism rather than metaplasia, one of the theories of spontaneous DPL. In an extremely unusual case, Sinha et al [15] reported a retained uterine fundus years after vaginal hysterectomy with presumed morcellation, again cautioning of the need to remove all fragments. Myomatous fragments have also been found growing in an abdominal wall incision after fragmentation [16], and a ‘‘lost’’ myoma by the liver requiring a repeat operation and retrieval has also been reported [17].
385
Kumar et al [18] suggested that DPL after morcellation is rare enough to make routine follow-up of asymptomatic women unnecessary. They state that consideration of oophorectomy to remove estrogenic stimulation in women with iatrogenic DPL is debatable, and we found no literature to support the performance of oophorectomy to prevent DPL. Leiomyosarcoma The rarity of leiomyosarcoma, as well as the lack of specific signs and symptoms to differentiate it preoperatively from leiomyoma, suggests that morcellation should not be avoided for fear of dissemination of a leiomyosarcoma [19]. In a study of 1091 uterine morcellations performed, Seidman et al [20] found that 1.2% of patients had an unexpected diagnosis of malignancy or uncertain malignant potential including endometrial stromal sarcoma, cellular leiomyoma, atypical leiomyoma, smooth muscle tumor of uncertain malignant potential, or leiomyosarcoma. Reviewing available follow-up procedures from a subset of 14 cases, both inhouse and consultation, in which there had been an unexpected diagnosis at morcellation, they found a 64.3% rate of disseminated disease, including from 1 cellular leiomyoma, 4 smooth muscle tumors of uncertain malignant potential, and 4 of 7 leiomyosarcomas. Only disseminated leiomyosarcoma was associated with death; however, the review included only a few years of follow-up. The nature of the specimen received by the pathology laboratory after morcellation of leiomyomas makes evaluation for malignancy, and in particular leiomyosarcoma, difficult. The gross appearance is so altered that sampling of an area that if intact may have been deemed suspect may not occur [21]. In addition, often pathologists resample a specimen if they are concerned, and submit additional sections for analysis. In a morcellated specimen, there is no way to know whether you are resampling the same ‘‘myoma.’’ Histologic features that define leiomyosarcoma include coagulative necrosis, hemorrhage, atypia, mitotic activity, and lack of circumscription. It is difficult to assess these in small fragments, in particular lack of circumscription. Anupama et al [22] reported the case of a 42-year-old woman who underwent morcellation of leiomyomas after being followed up for a lesion thought to be a myoma that had not grown in 8 years. Three months later she was found to have disseminated leiomyosarcoma, and died shortly thereafter. Re-review of the original pathologic report revealed that the lesion was actually a leiomyosarcoma. This case demonstrates several points. First, it is difficult to histopathologically diagnose a leiomyosarcoma from a morcellation specimen, and the benefit of hindsight may have aided the re-review. Second, after 8 years of no growth, the rapid tumor dissemination and fatal outcome suggest that the morcellation procedure contributed to the poor outcome. Dissemination of leiomyosarcoma via morcellation seems to worsen prognosis in reported series [20,23]. It is unclear in cases in which leiomyosarcoma is diagnosed initially
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after hysterectomy with morcellation whether adjuvant therapy is indicated. For intact hysterectomy specimens, simple hysterectomy is usually the treatment of choice for early-stage leiomyosarcoma [24]. Some oncologists recommend adjuvant chemotherapy, although this is controversial [23,25]. Chemotherapy also has been used in disseminated disease [25]. In cases of myomectomy, subsequent hysterectomy is clearly indicated. Einstein et al [26] recommend completion surgery, with staging for any unsuspected uterine malignancy, and have found that 15% of their cases were upstaged at repeat exploration, both leiomyosarcomas. Malignant lesions not up-staged seemed to have a good prognosis. In a series by Park et al [23], adjuvant therapy, usually chemotherapy, did not improve survival in patients with leiomyosarcoma discovered after morcellation. Leiomyosarcoma is a rare lesion, and there are no good preoperative indicators. However, morcellation of a leiomyosarcoma adversely affects disease-free and overall survival [23]. Endometriosis Theories of endometriosis development include lymphatic or vascular dissemination, retrograde menstruation, and metaplasia of coelomic epithelium. Uterine morcellation may disseminate endometrial implants and result in endometriosis, in a manner similar in mechanism to the theory of implanted retrograde menstruation. Endometriosis has developed in morcellator incisions [27] and in the pelvis [28]. Sepilian and Della Badia [28] noted that there was no endometriosis appreciated at the original surgery in their case, refuting worsening of preexisting endometriosis. In addition, the retroperitonealized cervix, which would have bled into that space if there had been residual endometrium, did not contain any endometrium. Cases have been reported in which these endometriotic implants have proliferated and become hyperplastic. In 1 case, atypical endometrial hyperplasia (complex hyperplasia with atypia) was documented in an endometriotic implant in a woman who had undergone supracervical laparoscopic hysterectomy with morcellation. The patient had no history of hyperplasia. She also had disseminated smooth muscle, adenomyosis, and usual endometriosis [29]. The authors suggested that this ectopic atypical hyperplasia had malignant potential, as does the uterine correlate. In a case-control study of women undergoing hysterectomy with or without morcellation, the rate of newly diagnosed endometriosis at repeat operation was the same in both groups. However, there were only 12 repeat surgeries in patients without endometriosis at first procedure, 5 with morcellation and 7 without [30]. The authors suggest that further study is warranted. Adenomyosis and Adenomyomatosis Although much less common than reports of disseminated leiomyomatosis, adenomyosis may also be disseminated via
Journal of Minimally Invasive Gynecology, Vol 21, No 3, May/June 2014
Fig. 1 Disseminated peritoneal adenomyomatosis. Note endometrial glandular epithelium and stroma embedded in hyperplastic smooth muscle.
morcellation, resulting in peritoneal nodules of adenomyosis. We recently treated a patient who had had adenomyosis at hysterectomy with morcellation and subsequently developed diffuse peritoneal nodules in the upper and lower abdomen, clinically mimicking malignancy (Fig. 1). Donnez et al [31] reported pelvic masses composed of adenomyosis in 8 of 1405 women who underwent repeat operation after laparoscopic subtotal hysterectomy. The original hysterectomies were all associated with adenomyosis. Endometrial Carcinoma Rivard et al [32] discussed challenges in detecting, staging, and grading endometrial carcinoma after morcellation. They evaluated 5 benign uteri and 5 uteri with endometrial adenocarcinoma via usual protocol, and then morcellated these uteri in vitro after initial pathologic evaluation. The same gynecologic pathologist misclassified both benign and malignant uteri, identifying only 4 of 5 cancers, undergrading 1, which depends on percentage of solid vs glandular tumor, and could not stage any of the morcellated specimens because of lack of a full-thickness uterine section available for depth. Schneider [33] reported the case of a premenopausal woman with a 1-year history of bleeding who underwent laparoscopic hysterectomy with morcellation and 5 months later was found to have a pelvic mass consistent with undifferentiated carcinoma. Although the initial specimen was read as benign, re-review showed clusters of malignant cells, and the author opined that a preoperative curettage may have been diagnostic. The patient had advanced disease, and despite adjuvant therapy died a year after hysterectomy. Morcellation poses challenges for the pathologist who evaluates the specimen. Inasmuch as the endometrial cavity often cannot be identified, Tam et al [34] suggest that
Heller and Cracchiolo.
Peritoneal Nodules after Uterine Morcellation
instilling dye into the uterine cavity before the procedure is helpful. Endometrial Stromal Sarcoma Reports of dissemination of the rare low-grade endometrial stromal sarcoma shortly after morcellation have been reported [35]. Park et al [36] compared outcomes in 27 patients with apparently early low-grade endometrial stromal sarcoma who did not undergo morcellation with 23 patients who did. Morcellation was associated with substantially higher risk of abdominopelvic recurrence and lower disease-free survival. Seven of 9 patients were saved after abdominopelvic recurrence via secondary surgery followed by chemotherapy or chemoradiation. Hence, overall survival was not significantly compromised in this small series of an unusual neoplasm. In conclusion, long-term complications of morcellation may include dissemination of both benign and malignant disease, leading to morbidity and rarely to death. Unexpected malignancy is a real but rare complication associated with uterine morcellation performed to treat presumed benign disease. This rare but possible complication must be conveyed as part of the informed consent process in patients at low risk who are candidates for a morcellation procedure. Future directions might include creation of a registry of patients requiring repeat operation because of recurrent peritoneal nodules after morcellation, to better assess the risk of this complication. References 1. Hagemann IS, Hagemann AR, LiVolsi VA, Montone KT, Chu CS. Risk of occult malignancy in morcellated hysterectomy: a case series. Int J Gynecol Pathol. 2011;30:476–483. 2. Nezhat C, Kho K. Iatrogenic myomas: new class of myomas? JMIG. 2010;17:544–550. 3. Paul PG, Koshy AK. Multiple peritoneal parasitic myomas after laparoscopic myomectomy and morcellation. Fertil Steril. 2006;85: 492–493. 4. LaCoursiere DY, Kennedy J, Hoffman CP. Retained fragments after total laparoscopic hysterectomy. JMIG. 2005;12:67–69. 5. Al-Talib A, Tulandi T. Pathophysiology and possible iatrogenic cause of leiomyomatosis peritonealis disseminata. Gynecol Obstet Invest. 2010;69:239–244. 6. Takeda A, Mori M, Sakai K, Mitsui T, Nakamura H. Parasitic peritoneal leiomyomatosis diagnosed 6 years after laparoscopic myomectomy with electric tissue morcellation: report of a case and review of the literature. JMIG. 2007;14:770–775. 7. Hales HA, Petersen CM, Jones KP, Quin JD. Leiomyomatosis peritonealis disseminata treated with a gonadotropin-releasing hormone agonist: a case report. Am J Obstet Gynecol. 1992;167:515–516. 8. Takeda T, Masuhara K, Kamiura S. Successful management of a leiomyomatosis peritonealis disseminata with an aromatase inhibitor. Obstet Gynecol. 2008;112:491–493. 9. Bekkers RL, Willemsen WN, Schijf CP, Massuger LF, Bulten J, Merkus JM. Leiomyomatosis peritonealis disseminata: does malignant transformation occur? a literature review. Gynecol Oncol. 1999;75: 158–163.
387 10. Ordulu Z, Cin PD, Chong WWS, et al. Disseminated peritoneal leiomyomatosis after laparoscopic supracervical hysterectomy with characteristic molecular cytogenetic findings of uterine leiomyoma. Genes Chromosomes Cancer. 2010;49:1152–1160. 11. Cucinella G, Granese R, Calagna G, Somigliana E, Perino A. Parasitic myomas after laparoscopic surgery: an emerging complication in the use of morcellator? description of four cases. Fertil Steril. 2011;96: e.90–e.96. 12. Lieng M, Istre O, Busund B, Qvigstad E. Severe complications caused by retained tissue in laparoscopic supracervical hysterectomy. JMIG. 2006;13:231–233. 13. Larraın D, Rabischong B, Khoo CK, Botchorishvili R, Canis M, Mage G. ‘‘Iatrogenic’’ parasitic myomas: unusual late complication of laparoscopic morcellation procedures. JMIG. 2010;17:719–724. 14. Epstein JH, Nejat EJ, Tsai T. Parasitic myomas after laparoscopic myomectomy: case report. Fertil Steril. 2009;91:932.e13–932.e14. 15. Sinha R, Lakhotia SM, Sundaram M, Manaktala G, Shah P, Mahajan C. Retained uterine fundus after vaginal hysterectomy. JMIG. 2010;17: 94–96. 16. Ostrzenski A. Uterine leiomyoma particle growing in an abdominalwall incision after laparoscopic retrieval. Obstet Gynecol. 1997;89: 853–854. 17. Hutchins FL Jr, Reinoehl EM. Retained myoma after laparoscopic supracervical hysterectomy with morcellation. J Am Assoc Gynecol Laparosc. 1998;5:293–295. 18. Kumar S, Sharma JB, Verma D, Gupta P, Roy KK, Malhotra N. Disseminated peritoneal leiomyomatosis: an unusual complication of laparoscopic myomectomy. Arch Gynecol Obstet. 2008;278:93–95. 19. Leung F, Terzibachian JJ, Gay C, et al. Hysterectomies performed for presumed leiomyomas: should the fear of leiomyosarcoma make us apprehend nonlaparotomic surgical routes [in French]. Gynecol Obstet Fertil. 2009;37:109–114. 20. Seidman MA, Oduyebo T, Muto MG, Crup CP, Nucci MR, Quade BJ. Peritoneal dissemination complicating morcellation of uterine mesenchymal neoplasms. PLoS One. 2013;7:e.50058. 21. Rekha W, Amita M, Sudeep G, Hemant T. Unexpected complication of uterine myoma morcellation. Aust N Z J Obstet Gynaecol. 2005;45: 248–258. 22. Anupama R, Ahmad SZ, Kuriakose S, Vijaykumar DK, Pavithran K, Seethalekshmy NV. Disseminated peritoneal leiomyosarcomas after laparoscopic ‘‘myomectomy’’ and morcellation. JMIG. 2011;18: 386–389. 23. Park JY, Park SK, Kim DY, et al. The impact of tumor morcellation during surgery on the prognosis of patients with apparently early uterine leiomyosarcoma. Gynecol Oncol. 2011;122:255–259. 24. Amant F, Coosemans A, Debiec-Rychter M, Timmerman D, Vergote I. Clinical management of uterine sarcomas. Lancet Oncol. 2009;10: 1188–1198. 25. Hadoux J, Morice P, Lhomme C, et al. Uterine leiomyosarcoma: epidemiology, pathology, biology, diagnosis, prognosis and treatment. Bull Cancer. 2013;100:903–915. 26. Einstein MH, Barakat RR, Chi DS, et al. Management of uterine malignancy found incidentally after supracervical hysterectomy or uterine morcellation for presumed benign disease. Int J Gynecol Cancer. 2008;18:1065–1070. 27. Brown RL. Iatrogenic endometriosis caused by uterine morcellation during a supracervical hysterectomy. Obstet Gynecol. 2004;103:583. 28. Sepilian V, Della Badia C. Iatrogenic endometriosis caused by uterine morcellation during a supracervical hysterectomy. Obstet Gynecol. 2003;102:1125–1127. 29. Kill LM, Kapetanakis V, McCullough AE, Magrina JF. Progression of pelvic implants to complex atypical endometrial hyperplasia after uterine morcellation. Obstet Gynecol. 2011;117:447–449. 30. Schuster MW, Wheeler TL, Richter HE. Endometriosis after laparoscopic supracervical hysterectomy with uterine morcellator: a case control study. JMIG. 2013;19:183–187.
388 31. Donnez O, Squifflet J, Leconte I, Jadoul P, Donnez J. Posthysterectomy pelvic adenomyotic masses observed in 8 cases out of a series of 1405 laparoscopic subtotal hysterectomies. JMIG. 2007;14: 156–160. 32. Rivard C, Salhadar A, Kenton K. New challenges in detecting, grading and staging endometrial cancer after uterine morcellation. JMIG. 2013; 19:313–316. 33. Schneider A. Recurrence of unclassifiable uterine cancer after modified laparoscopic hysterectomy with morcellation. Am J Obstet Gynecol. 1997;177:478–479.
Journal of Minimally Invasive Gynecology, Vol 21, No 3, May/June 2014 34. Tam T, Harkins G, Caldwell T, Zaino R, Hazard D. Endometrial dye instillation: a novel approach to histopathologic evaluation of morcellated hysterectomy specimens. JMIG. 2013;20:667–671. 35. Badia CD, Karini H. Endometrial stromal sarcoma diagnosed after uterine morcellation in laparoscopic supracervical hysterectomy. JMIG. 2010;17:791–793. 36. Park JY, Kim DY, Kim JH, Kim YM, Kim YT, Nam JH. The impact of tumor morcellation during surgery on the outcomes of patients with apparently early low-grade endometrial stromal sarcoma of the uterus. Ann Surg Oncol. 2011;18:3453–3461.
Peritoneal Nodules after Laparoscopic Surgery With Uterine Morcellation: Review of a Rare Complication Debra S. Heller, MD*, and Bernadette Cracchiolo, MD, MPH From the Departments of Pathology and Laboratory Medicine (Dr. Heller), and Obstetrics, Gynecology, and Women’s Health (Drs. Heller and Cracchiolo), Rutgers–New Jersey Medical School, Newark, New Jersey (both authors).
ABSTRACT The risk of occult malignancy being present at the time of uterine morcellation has been estimated to be about 1%. Dissemination of both benign and malignant disease may occur after morcellation, leading to a variety of peritoneal nodules. These lesions are reviewed. Journal of Minimally Invasive Gynecology (2014) 21, 384–388 Ó 2014 AAGL. All rights reserved. Keywords:
DISCUSS
Adenomyosis; Endometriosis; Leiomyoma; Leiomyosarcoma; Uterine neoplasms
You can discuss this article with its authors and with other AAGL members at http://www.AAGL.org/jmig-21-4-JMIG-D-13-00604
Use your Smartphone to scan this QR code and connect to the discussion forum for this article now* * Download a free QR Code scanner by searching for ‘‘QR scanner’’ in your smartphone’s app store or app marketplace.
Morcellation of uterine tissue, in the course of hysterectomy or myomectomy, is part of the arsenal of minimally invasive gynecologic procedures. It enables removal of tissue fragments through a smaller abdominal wall incision or a colpotomy incision. Rarely, viable tissue fragments may attach to the peritoneum-lined surfaces in the pelvis and even in the upper abdomen, and nodules may develop. In addition, there may be limitations on the ability to assess criteria for malignancy at pathologic evaluation of the surgical specimen, as well as concern of dissemination of unsuspected malignant disease. On the basis of finding 1 possible epithelioid trophoblastic tumor in 101 morcellated specimens, Hagemann et al [1] estimated the risk of occult malignancy at 1%. Although such cases are uncommon, minimally invasive surgeons should be aware of this potential complication. A systematic review of the literature is presented herein.
The authors declare no conflicts of interest. Corresponding author: Debra S. Heller, MD, Department of Pathology, Rutgers–New Jersey Medical School, UH E158, 185 S Orange Ave, Newark, NJ 07103. E-mail: [email protected] Submitted November 6, 2013. Accepted for publication January 2, 2014. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ - see front matter Ó 2014 AAGL. All rights reserved. http://dx.doi.org/10.1016/j.jmig.2014.01.003
Leiomyomas and Subsequent Parasitic Leiomyomas and Iatrogenic Diffuse Peritoneal Leiomyomatosis Parasitic leiomyoma has traditionally been thought to be secondary to a pedunculated subserosal leiomyoma that lost its blood supply and developed a new one at the parasitic site. More recently, occasional cases have been reported after laparoscopic surgery with morcellation of leiomyomas [2]. In addition to single lesions, diffuse peritoneal leiomyomatosis (DPL) has occurred. Symptoms of DPL include urinary retention [3], dysuria, and pelvic pain [4]. DPL is a rare condition, first described in 1952. In a literature search by Al-Talib and Tulandi [5], 132 cases were found in the English literature, and they attributed 5 of these to an iatrogenic cause after morcellation. Since then, scattered case reports have increased the reported numbers in the literature. Relationship to hormonal stimulation is supported by estrogen and progesterone receptors in the lesions and by the occurrence of cases in an increased hormonal milieu such as pregnancy, oral contraceptive use, hormone replacement therapy, tamoxifen administration, estrogen-secreting tumors, or ovarian stimulation [5]. Takeda et al [6] reported DPL diagnosed 6 years after laparoscopic myomectomy with morcellation. The patient, aged 39 years at the time of her second presentation, was found to have asymptomatic lower abdominal nodules ranging from 1 to 6 cm attached to the peritoneal surfaces including the round ligament, omentum, vesicouterine pouch, Douglas pouch, and pelvic sidewall.
Heller and Cracchiolo.
Peritoneal Nodules after Uterine Morcellation
The uterus demonstrated no important pathologic findings. The nodules were resected during laparoscopy. Histopathologic analysis revealed that the lesions were histologically consistent with leiomyomas. At immunohistochemistry, both the initial and recurrent lesions stained positive for progesterone receptor. Other studies have demonstrated both estrogen and progesterone receptors, which along with the premenopausal stage of most patients suggests a role for hormonal stimulation of disseminated tissue [5] Regression has been reported with administration of gonadotropin-releasing hormone agonist [7] or aromatase inhibitor [8]. Rarely, DPL has undergone malignant transformation [9]. Ordulu et al [10] reported a similar case after laparoscopic supracervical hysterectomy with morcellation of leiomyomas in which the nodules developed 7 years after the initial surgery. The authors demonstrated an association between the chromosomal alterations of both the original leiomyoma tissue and the DPL, with both having a 3q deletion. They also noted the association of DPL in premenopausal women and suggested that the condition is related to estrogen and progesterone stimulation. Cucinella et al [11] reported 4 DPL cases after morcellation of myomas, for a prevalence of 1.2% during their 3-year study. Two of the patients had symptoms, and 2 did not. The authors recommended inspection and irrigation of the abdominopelvic cavity at the end of the surgical procedure. Short-term complications of retained uterine tissue after morcellation have also been reported, including infectious complications with necrosis of the retained tissue, requiring a repeat operation [12]. Of interest, the fastest recurrence, at 24 months, was in a patient with an intervening pregnancy, further supporting hormonal stimulation as contributory. Smooth muscle nodules can manifest many years after morcellation. One of the cases reported by Larraın et al [13] manifested 16 years after initial laparoscopic morcellation. Dissemination of myoma fragments is thought to be the underlying cause of DPL. Epstein et al [14] reviewed the video footage of the original myomectomy in their patient with DPL and noted dispersed pieces of myoma in the pelvis. They advised careful removal of all fragments [14]. In the case reported by Paul et al [3], a 28-year-old woman was found to have multiple parasitic leiomyomas at 2½ years after morcellation. The location of one of the nodules on the parietal peritoneum at the laparoscopy port site lends support to iatrogenic dissemination. Of interest, in the case reported by LaCoursiere et al [4], cervical tissue also identified with smooth muscle fragments favors including implantation as the mechanism rather than metaplasia, one of the theories of spontaneous DPL. In an extremely unusual case, Sinha et al [15] reported a retained uterine fundus years after vaginal hysterectomy with presumed morcellation, again cautioning of the need to remove all fragments. Myomatous fragments have also been found growing in an abdominal wall incision after fragmentation [16], and a ‘‘lost’’ myoma by the liver requiring a repeat operation and retrieval has also been reported [17].
385
Kumar et al [18] suggested that DPL after morcellation is rare enough to make routine follow-up of asymptomatic women unnecessary. They state that consideration of oophorectomy to remove estrogenic stimulation in women with iatrogenic DPL is debatable, and we found no literature to support the performance of oophorectomy to prevent DPL. Leiomyosarcoma The rarity of leiomyosarcoma, as well as the lack of specific signs and symptoms to differentiate it preoperatively from leiomyoma, suggests that morcellation should not be avoided for fear of dissemination of a leiomyosarcoma [19]. In a study of 1091 uterine morcellations performed, Seidman et al [20] found that 1.2% of patients had an unexpected diagnosis of malignancy or uncertain malignant potential including endometrial stromal sarcoma, cellular leiomyoma, atypical leiomyoma, smooth muscle tumor of uncertain malignant potential, or leiomyosarcoma. Reviewing available follow-up procedures from a subset of 14 cases, both inhouse and consultation, in which there had been an unexpected diagnosis at morcellation, they found a 64.3% rate of disseminated disease, including from 1 cellular leiomyoma, 4 smooth muscle tumors of uncertain malignant potential, and 4 of 7 leiomyosarcomas. Only disseminated leiomyosarcoma was associated with death; however, the review included only a few years of follow-up. The nature of the specimen received by the pathology laboratory after morcellation of leiomyomas makes evaluation for malignancy, and in particular leiomyosarcoma, difficult. The gross appearance is so altered that sampling of an area that if intact may have been deemed suspect may not occur [21]. In addition, often pathologists resample a specimen if they are concerned, and submit additional sections for analysis. In a morcellated specimen, there is no way to know whether you are resampling the same ‘‘myoma.’’ Histologic features that define leiomyosarcoma include coagulative necrosis, hemorrhage, atypia, mitotic activity, and lack of circumscription. It is difficult to assess these in small fragments, in particular lack of circumscription. Anupama et al [22] reported the case of a 42-year-old woman who underwent morcellation of leiomyomas after being followed up for a lesion thought to be a myoma that had not grown in 8 years. Three months later she was found to have disseminated leiomyosarcoma, and died shortly thereafter. Re-review of the original pathologic report revealed that the lesion was actually a leiomyosarcoma. This case demonstrates several points. First, it is difficult to histopathologically diagnose a leiomyosarcoma from a morcellation specimen, and the benefit of hindsight may have aided the re-review. Second, after 8 years of no growth, the rapid tumor dissemination and fatal outcome suggest that the morcellation procedure contributed to the poor outcome. Dissemination of leiomyosarcoma via morcellation seems to worsen prognosis in reported series [20,23]. It is unclear in cases in which leiomyosarcoma is diagnosed initially
386
after hysterectomy with morcellation whether adjuvant therapy is indicated. For intact hysterectomy specimens, simple hysterectomy is usually the treatment of choice for early-stage leiomyosarcoma [24]. Some oncologists recommend adjuvant chemotherapy, although this is controversial [23,25]. Chemotherapy also has been used in disseminated disease [25]. In cases of myomectomy, subsequent hysterectomy is clearly indicated. Einstein et al [26] recommend completion surgery, with staging for any unsuspected uterine malignancy, and have found that 15% of their cases were upstaged at repeat exploration, both leiomyosarcomas. Malignant lesions not up-staged seemed to have a good prognosis. In a series by Park et al [23], adjuvant therapy, usually chemotherapy, did not improve survival in patients with leiomyosarcoma discovered after morcellation. Leiomyosarcoma is a rare lesion, and there are no good preoperative indicators. However, morcellation of a leiomyosarcoma adversely affects disease-free and overall survival [23]. Endometriosis Theories of endometriosis development include lymphatic or vascular dissemination, retrograde menstruation, and metaplasia of coelomic epithelium. Uterine morcellation may disseminate endometrial implants and result in endometriosis, in a manner similar in mechanism to the theory of implanted retrograde menstruation. Endometriosis has developed in morcellator incisions [27] and in the pelvis [28]. Sepilian and Della Badia [28] noted that there was no endometriosis appreciated at the original surgery in their case, refuting worsening of preexisting endometriosis. In addition, the retroperitonealized cervix, which would have bled into that space if there had been residual endometrium, did not contain any endometrium. Cases have been reported in which these endometriotic implants have proliferated and become hyperplastic. In 1 case, atypical endometrial hyperplasia (complex hyperplasia with atypia) was documented in an endometriotic implant in a woman who had undergone supracervical laparoscopic hysterectomy with morcellation. The patient had no history of hyperplasia. She also had disseminated smooth muscle, adenomyosis, and usual endometriosis [29]. The authors suggested that this ectopic atypical hyperplasia had malignant potential, as does the uterine correlate. In a case-control study of women undergoing hysterectomy with or without morcellation, the rate of newly diagnosed endometriosis at repeat operation was the same in both groups. However, there were only 12 repeat surgeries in patients without endometriosis at first procedure, 5 with morcellation and 7 without [30]. The authors suggest that further study is warranted. Adenomyosis and Adenomyomatosis Although much less common than reports of disseminated leiomyomatosis, adenomyosis may also be disseminated via
Journal of Minimally Invasive Gynecology, Vol 21, No 3, May/June 2014
Fig. 1 Disseminated peritoneal adenomyomatosis. Note endometrial glandular epithelium and stroma embedded in hyperplastic smooth muscle.
morcellation, resulting in peritoneal nodules of adenomyosis. We recently treated a patient who had had adenomyosis at hysterectomy with morcellation and subsequently developed diffuse peritoneal nodules in the upper and lower abdomen, clinically mimicking malignancy (Fig. 1). Donnez et al [31] reported pelvic masses composed of adenomyosis in 8 of 1405 women who underwent repeat operation after laparoscopic subtotal hysterectomy. The original hysterectomies were all associated with adenomyosis. Endometrial Carcinoma Rivard et al [32] discussed challenges in detecting, staging, and grading endometrial carcinoma after morcellation. They evaluated 5 benign uteri and 5 uteri with endometrial adenocarcinoma via usual protocol, and then morcellated these uteri in vitro after initial pathologic evaluation. The same gynecologic pathologist misclassified both benign and malignant uteri, identifying only 4 of 5 cancers, undergrading 1, which depends on percentage of solid vs glandular tumor, and could not stage any of the morcellated specimens because of lack of a full-thickness uterine section available for depth. Schneider [33] reported the case of a premenopausal woman with a 1-year history of bleeding who underwent laparoscopic hysterectomy with morcellation and 5 months later was found to have a pelvic mass consistent with undifferentiated carcinoma. Although the initial specimen was read as benign, re-review showed clusters of malignant cells, and the author opined that a preoperative curettage may have been diagnostic. The patient had advanced disease, and despite adjuvant therapy died a year after hysterectomy. Morcellation poses challenges for the pathologist who evaluates the specimen. Inasmuch as the endometrial cavity often cannot be identified, Tam et al [34] suggest that
Heller and Cracchiolo.
Peritoneal Nodules after Uterine Morcellation
instilling dye into the uterine cavity before the procedure is helpful. Endometrial Stromal Sarcoma Reports of dissemination of the rare low-grade endometrial stromal sarcoma shortly after morcellation have been reported [35]. Park et al [36] compared outcomes in 27 patients with apparently early low-grade endometrial stromal sarcoma who did not undergo morcellation with 23 patients who did. Morcellation was associated with substantially higher risk of abdominopelvic recurrence and lower disease-free survival. Seven of 9 patients were saved after abdominopelvic recurrence via secondary surgery followed by chemotherapy or chemoradiation. Hence, overall survival was not significantly compromised in this small series of an unusual neoplasm. In conclusion, long-term complications of morcellation may include dissemination of both benign and malignant disease, leading to morbidity and rarely to death. Unexpected malignancy is a real but rare complication associated with uterine morcellation performed to treat presumed benign disease. This rare but possible complication must be conveyed as part of the informed consent process in patients at low risk who are candidates for a morcellation procedure. Future directions might include creation of a registry of patients requiring repeat operation because of recurrent peritoneal nodules after morcellation, to better assess the risk of this complication. References 1. Hagemann IS, Hagemann AR, LiVolsi VA, Montone KT, Chu CS. Risk of occult malignancy in morcellated hysterectomy: a case series. Int J Gynecol Pathol. 2011;30:476–483. 2. Nezhat C, Kho K. Iatrogenic myomas: new class of myomas? JMIG. 2010;17:544–550. 3. Paul PG, Koshy AK. Multiple peritoneal parasitic myomas after laparoscopic myomectomy and morcellation. Fertil Steril. 2006;85: 492–493. 4. LaCoursiere DY, Kennedy J, Hoffman CP. Retained fragments after total laparoscopic hysterectomy. JMIG. 2005;12:67–69. 5. Al-Talib A, Tulandi T. Pathophysiology and possible iatrogenic cause of leiomyomatosis peritonealis disseminata. Gynecol Obstet Invest. 2010;69:239–244. 6. Takeda A, Mori M, Sakai K, Mitsui T, Nakamura H. Parasitic peritoneal leiomyomatosis diagnosed 6 years after laparoscopic myomectomy with electric tissue morcellation: report of a case and review of the literature. JMIG. 2007;14:770–775. 7. Hales HA, Petersen CM, Jones KP, Quin JD. Leiomyomatosis peritonealis disseminata treated with a gonadotropin-releasing hormone agonist: a case report. Am J Obstet Gynecol. 1992;167:515–516. 8. Takeda T, Masuhara K, Kamiura S. Successful management of a leiomyomatosis peritonealis disseminata with an aromatase inhibitor. Obstet Gynecol. 2008;112:491–493. 9. Bekkers RL, Willemsen WN, Schijf CP, Massuger LF, Bulten J, Merkus JM. Leiomyomatosis peritonealis disseminata: does malignant transformation occur? a literature review. Gynecol Oncol. 1999;75: 158–163.
387 10. Ordulu Z, Cin PD, Chong WWS, et al. Disseminated peritoneal leiomyomatosis after laparoscopic supracervical hysterectomy with characteristic molecular cytogenetic findings of uterine leiomyoma. Genes Chromosomes Cancer. 2010;49:1152–1160. 11. Cucinella G, Granese R, Calagna G, Somigliana E, Perino A. Parasitic myomas after laparoscopic surgery: an emerging complication in the use of morcellator? description of four cases. Fertil Steril. 2011;96: e.90–e.96. 12. Lieng M, Istre O, Busund B, Qvigstad E. Severe complications caused by retained tissue in laparoscopic supracervical hysterectomy. JMIG. 2006;13:231–233. 13. Larraın D, Rabischong B, Khoo CK, Botchorishvili R, Canis M, Mage G. ‘‘Iatrogenic’’ parasitic myomas: unusual late complication of laparoscopic morcellation procedures. JMIG. 2010;17:719–724. 14. Epstein JH, Nejat EJ, Tsai T. Parasitic myomas after laparoscopic myomectomy: case report. Fertil Steril. 2009;91:932.e13–932.e14. 15. Sinha R, Lakhotia SM, Sundaram M, Manaktala G, Shah P, Mahajan C. Retained uterine fundus after vaginal hysterectomy. JMIG. 2010;17: 94–96. 16. Ostrzenski A. Uterine leiomyoma particle growing in an abdominalwall incision after laparoscopic retrieval. Obstet Gynecol. 1997;89: 853–854. 17. Hutchins FL Jr, Reinoehl EM. Retained myoma after laparoscopic supracervical hysterectomy with morcellation. J Am Assoc Gynecol Laparosc. 1998;5:293–295. 18. Kumar S, Sharma JB, Verma D, Gupta P, Roy KK, Malhotra N. Disseminated peritoneal leiomyomatosis: an unusual complication of laparoscopic myomectomy. Arch Gynecol Obstet. 2008;278:93–95. 19. Leung F, Terzibachian JJ, Gay C, et al. Hysterectomies performed for presumed leiomyomas: should the fear of leiomyosarcoma make us apprehend nonlaparotomic surgical routes [in French]. Gynecol Obstet Fertil. 2009;37:109–114. 20. Seidman MA, Oduyebo T, Muto MG, Crup CP, Nucci MR, Quade BJ. Peritoneal dissemination complicating morcellation of uterine mesenchymal neoplasms. PLoS One. 2013;7:e.50058. 21. Rekha W, Amita M, Sudeep G, Hemant T. Unexpected complication of uterine myoma morcellation. Aust N Z J Obstet Gynaecol. 2005;45: 248–258. 22. Anupama R, Ahmad SZ, Kuriakose S, Vijaykumar DK, Pavithran K, Seethalekshmy NV. Disseminated peritoneal leiomyosarcomas after laparoscopic ‘‘myomectomy’’ and morcellation. JMIG. 2011;18: 386–389. 23. Park JY, Park SK, Kim DY, et al. The impact of tumor morcellation during surgery on the prognosis of patients with apparently early uterine leiomyosarcoma. Gynecol Oncol. 2011;122:255–259. 24. Amant F, Coosemans A, Debiec-Rychter M, Timmerman D, Vergote I. Clinical management of uterine sarcomas. Lancet Oncol. 2009;10: 1188–1198. 25. Hadoux J, Morice P, Lhomme C, et al. Uterine leiomyosarcoma: epidemiology, pathology, biology, diagnosis, prognosis and treatment. Bull Cancer. 2013;100:903–915. 26. Einstein MH, Barakat RR, Chi DS, et al. Management of uterine malignancy found incidentally after supracervical hysterectomy or uterine morcellation for presumed benign disease. Int J Gynecol Cancer. 2008;18:1065–1070. 27. Brown RL. Iatrogenic endometriosis caused by uterine morcellation during a supracervical hysterectomy. Obstet Gynecol. 2004;103:583. 28. Sepilian V, Della Badia C. Iatrogenic endometriosis caused by uterine morcellation during a supracervical hysterectomy. Obstet Gynecol. 2003;102:1125–1127. 29. Kill LM, Kapetanakis V, McCullough AE, Magrina JF. Progression of pelvic implants to complex atypical endometrial hyperplasia after uterine morcellation. Obstet Gynecol. 2011;117:447–449. 30. Schuster MW, Wheeler TL, Richter HE. Endometriosis after laparoscopic supracervical hysterectomy with uterine morcellator: a case control study. JMIG. 2013;19:183–187.
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Journal of Minimally Invasive Gynecology, Vol 21, No 3, May/June 2014 34. Tam T, Harkins G, Caldwell T, Zaino R, Hazard D. Endometrial dye instillation: a novel approach to histopathologic evaluation of morcellated hysterectomy specimens. JMIG. 2013;20:667–671. 35. Badia CD, Karini H. Endometrial stromal sarcoma diagnosed after uterine morcellation in laparoscopic supracervical hysterectomy. JMIG. 2010;17:791–793. 36. Park JY, Kim DY, Kim JH, Kim YM, Kim YT, Nam JH. The impact of tumor morcellation during surgery on the outcomes of patients with apparently early low-grade endometrial stromal sarcoma of the uterus. Ann Surg Oncol. 2011;18:3453–3461.
