Original Article Gynecol Obstet Invest 2015;79:168–171 DOI: 10.1159/000369996
Received: November 14, 2013 Accepted after revision: November 18, 2014 Published online: February 3, 2015
Massive Cystic Degeneration of a Uterine Leiomyoma in a Patient with Autosomal Dominant Polycystic Kidney Disease Takuji Tomimatsu a Mika Sugihara a Takafumi Nakamura a Naoki Kashihara b Koichiro Shimoya a Departments of a Obstetrics and Gynecology and b Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan
Key Words Autosomal dominant polycystic kidney disease · Uterine cyst · Cyst aspiration
Abstract Background: A uterine cyst occurring as an extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD) is extremely rare. Case: A 46-year-old Japanese woman was referred with a large abdominal mass causing severe abdominal distension. A large uterine cyst as an extrarenal manifestation of ADPKD was strongly suspected. First, we managed this patient by aspirating the cyst fluid through a small laparotomy. A year later, the cyst recurred and the patient underwent hysterectomy. Massive cystic degeneration of a uterine leiomyoma was diagnosed histologically. Conclusion: We described the rare case of massive cystic degeneration of a uterine leiomyoma in a patient with ADPKD, in which a causal relationship was suspected. © 2015 S. Karger AG, Basel
Introduction
Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disease characterized by the formation of multiple cysts in the kidney as well as © 2015 S. Karger AG, Basel 0378–7346/15/0793–0168$39.50/0 E-Mail [email protected] www.karger.com/goi
in extrarenal organs such as the liver and pancreas [1]. The occurrence of a uterine cyst as an extrarenal manifestation of ADPKD is extremely rare. To our knowledge, only 1 case of a uterine cyst in an ADPKD patient has been reported in the English-language literature [2]. Here, we report a case of an ADPKD patient with massive cystic degeneration of a uterine leiomyoma. Case Report A 46-year-old woman was referred with a large abdominal mass, which she had noticed more than a year ago. Her periods were irregular, occurring every 30–45 days, without severe dysmenorrhea and menorrhagia. She had a history of two spontaneous abortions and had undergone dilatation and curettage at ages 38 and 39 years. She could not conceive after these abortions, but she did not consult a doctor until the present symptom occurred. Abdominal examination revealed a tense mass ranging from the lower to the upper abdomen and causing severe abdominal distension. An ultrasound examination of her abdomen revealed a cystic mass with multiple membranous structures, which were wavy in response to manipulation of the mass (fig. 1). A magnetic resonance imaging (MRI) T2weighted image showed a large and well-circumscribed high-signal mass (15.5 × 13.5 cm) located in the uterus (fig. 2). Computed tomography examination revealed a large and mostly cystic uterine mass (fig. 3a) with multiple renal and hepatic cysts (fig. 3b). The patient’s family history was remarkable for ADPKD. Her parents are married first cousins, and both parents as well as their families have a history of ADPKD. The patient’s older sister had multiple renal and hepatic cysts. A diagnosis of ADPKD with a
Takuji Tomimatsu, MD Department of Obstetrics and Gynecology Kawasaki Medical School 577, Matsushima, Kurashiki, Okayama 701-0192 (Japan) E-Mail tomimatsu @ med.kawasaki-m.ac.jp
Fig. 1. Ultrasound image of the abdomen showing a cystic mass
with multiple membranous structures.
a
Fig. 2. MRI T2-weighted image showing a large and well-circumscribed high-signal mass in the uterus.
b
Fig. 3. CT images showing a large cystic uterine mass (a) and multiple renal and hepatic cysts (b).
large uterine cyst as an extrarenal manifestation was strongly suspected. The patient was not hypertensive, and her renal function was normal at the time of referral. Although a hysterectomy was recommended to relieve her severe abdominal distension and to rule out the possibility of malignancies, the decision to perform aspiration through a small laparotomy was made because the patient opted for a fertility-sparing treatment. Following the prophylactic administration of ciprofloxacin, a second-generation fluoroquinolone, a 2-cm incision was made below the umbilicus, and a 5-mm SAND balloon catheter (Hakko Medical, Tokyo, Japan) was inserted through the uterine wall under direct visual guidance. The cyst wall was sandwiched between 2 inflated balloons, and the cyst was carefully aspirated. Because aspiration was difficult, it was stopped when 1,360 ml of serous fluid had been aspirated. Sclerotherapy was not performed in consideration of potential adverse effects on the endometrium. The operative time was 24 min, and the postoperative hospital stay was 3 days. The patient’s abdominal distension resolved after the
operation, and an abdominal ultrasound examination revealed that the uterine cyst was reduced to almost half of its previous size. Cytological analysis of the uterine cyst fluid was performed using a cell block technique as this technique has been reported to increase the sensitivity of malignancy detection and to help better demonstrate the cellular architectural pattern [3]. The aspirated fluid contained no malignant cells but only scattered histiocytes and inflammatory cells such as lymphocytes and neutrophils. A year later, the patient visited our hospital for the first time since the aspiration. We found that the uterine cyst had increased in size since the aspiration and was causing severe distension. The patient consented to total abdominal hysterectomy, and the giant uterus, weighting 3.8 kg, was removed (fig. 4a). We found a large smooth mass inside the uterine cavity (fig. 4b). The inside of the uterine mass, which contained 2,100 ml of clear serous fluid, was multilocular in nature (fig. 4c). The operative time was 109 min, blood loss was 96 ml, and the postoperative hospital stay was 7 days. Histopathological examination revealed cystic degeneration of a uterine leiomyoma.
Uterine Cyst in a Patient with ADPKD
Gynecol Obstet Invest 2015;79:168–171 DOI: 10.1159/000369996
169
b
Color version available online
a
c
Fig. 4. a Gross appearance of the uterus. b Large smooth mass inside the uterine cavity. c The inside of the uterine mass.
Discussion
ADPKD is a systemic disorder with cystic manifestations in the kidneys, liver, pancreas, seminal vesicles, and meninges [1]. Although ovarian cysts are occasionally encountered in patients with ADPKD, this association has not proved to be significant [4]. In 85–90% of cases, ADPKD results from a mutation in the PKD1 gene (polycystic kidney disease 1), which encodes polycystin-1, and in the remaining 10–15% of cases from a mutation in the PKD2 gene (polycystic kidney disease 2), which encodes polycystin-2. Both proteins are localized to the primary cilia and control the channel activity of the polycystin signaling complex, which may play a part in coordinating the cellular response to changes in extracellular fluid flow. Although the mechanisms of cyst formation in ADPKD patients remain unclear, recent evidence suggests that the dysfunction of primary cilia, called ‘ciliopathy’, plays a central role in ADPKD cystogenesis [5]. The massive uterine cyst in the present case was a manifestation of cystic degeneration of a uterine leiomyoma, which is present in up to 50% of leiomyomas, mostly in a focal form. Although the exact etiology of leiomyoma and its cystic degeneration is unknown [6, 7], diffuse cystic degeneration is extremely rare, and the largest simple cystic degenerative uterine leiomyoma reported measured 10 cm [8]. To our knowledge, this is the largest case of cystic degeneration of a uterine leiomyoma yet reported. The differential diagnosis might include cystic adenomyosis [9] or congenital Müllerian cyst [10]. Notably, the MRI findings in our case were very similar to those in a case of a giant cystic adenomyosis reported by Koga et al. [9]. 170
Gynecol Obstet Invest 2015;79:168–171 DOI: 10.1159/000369996
Percutaneous cyst aspiration and sclerosis with alcohol or minocycline under ultrasound guidance is generally performed for the treatment of renal and hepatic cysts in ADPKD patients [11]. We performed cyst aspiration through a small laparotomy using a thick catheter as we feared that uterine wall contraction and the reduction in uterine size along with cyst aspiration and the many membranous structures within the cyst might prevent complete cyst aspiration. Even so, cyst aspiration was incomplete because of aspiration difficulty, probably owing to the membranous structures inside the cyst. Cyst infection is a frequent and serious complication that often follows the aspiration of renal cysts in ADPKD patients. Therefore, uterine cyst aspiration was performed after the prophylactic administration of a fluoroquinolone, which is usually favored because the lipophilic properties of fluoroquinolone increase diffusion to the inside of the cyst. However, unlike in the case of percutaneous renal cyst aspiration, prophylactic antibiotic administration might not be needed in this case as this procedure was performed under clean and aseptic conditions. We also thought that transvaginal cyst aspiration might carry an increased risk of infection. Here, we described the rare case of massive cystic degeneration of a uterine leiomyoma in a patient with ADPKD, in which a causal relationship was strongly suspected. In ADPKD patients, every cell carries a mutated allele of either PKD1 or PKD2, which is thought to account for the systemic cyst formation characteristic of this genetic disorder. Although we do not know whether this patient had a preexisting leiomyoma, there is a possibility that the genetic mutations play a role in the cystic degeneration of such tumors. Tomimatsu/Sugihara/Nakamura/ Kashihara/Shimoya
References 1 Grantham JJ, Nair V, Winklhofer F: Cystic disease of the kidney; in Brenner BM (ed): The Kidney, ed 6. Philadelphia, WB Saunders, 2000, pp 1701–1710. 2 Okeahialam BN, Pam SD, Ekedigwe JE, Ekwempu CC: Familial polycystic kidney disease in Nigeria: a report of two cases. West Afr J Med 2006;25:249–251. 3 Thapar M1, Mishra RK, Sharma A, Goyal V, Goyal V: Critical analysis of cell block versus smear examination in effusions. J Cytol 2009; 26:60–64. 4 Heinonen PK, Vuento M, Maunola M, AlaHouhala I: Ovarian manifestations in women with autosomal dominant polycystic kidney disease. Am J Kidney Dis 2002;40:504–507.
Uterine Cyst in a Patient with ADPKD
5 Mochizuki T, Tsuchiya K, Nitta K: Autosomal dominant polycystic kidney disease: recent advances in pathogenesis and potential therapies. Clin Exp Nephrol 2013;17:317–326. 6 Shen Y, Ren ML, Xu J, Xu Q, Ding YQ, Wu ZC, Zhang HB, Huang XX, Cai YL: A multicenter case-control study on screening of single nucleotide polymorphisms in estrogenmetabolizing enzymes and susceptibility to uterine leiomyoma in Han Chinese. Gynecol Obstet Invest 2014;77:224–230. 7 Csatlós E, Rigó J Jr, Laky M, Joó JG: Gene expression patterns of insulin-like growth factor 2 in human uterine fibroid tissues: a genetic study with clinical correlations. Gynecol Obstet Invest 2013;75:185–189.
8 Yarwood RL, Arroyo E: Cystic degeneration of a uterine leiomyoma masquerading as a postmenopausal ovarian cyst. A case report. J Reprod Med 1999;44:649–652. 9 Koga K, Osuga Y, Hiroi H, Oishi H, Kugu K, Yano T, Taketani Y: Images in reproductive medicine. A case of giant cystic adenomyosis. Fertil Steril 2006;85:748–749. 10 Acién P, Acién M, Fernández F, José Mayol M, Aranda I: The cavitated accessory uterine mass: a Müllerian anomaly in women with an otherwise normal uterus. Obstet Gynecol 2010;116:1101–1109. 11 Chandok N: Polycystic liver disease: a clinical review. Ann Hepatol 2012;11:819–826.
Gynecol Obstet Invest 2015;79:168–171 DOI: 10.1159/000369996
171
Copyright: S. Karger AG, Basel 2015. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
Received: November 14, 2013 Accepted after revision: November 18, 2014 Published online: February 3, 2015
Massive Cystic Degeneration of a Uterine Leiomyoma in a Patient with Autosomal Dominant Polycystic Kidney Disease Takuji Tomimatsu a Mika Sugihara a Takafumi Nakamura a Naoki Kashihara b Koichiro Shimoya a Departments of a Obstetrics and Gynecology and b Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan
Key Words Autosomal dominant polycystic kidney disease · Uterine cyst · Cyst aspiration
Abstract Background: A uterine cyst occurring as an extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD) is extremely rare. Case: A 46-year-old Japanese woman was referred with a large abdominal mass causing severe abdominal distension. A large uterine cyst as an extrarenal manifestation of ADPKD was strongly suspected. First, we managed this patient by aspirating the cyst fluid through a small laparotomy. A year later, the cyst recurred and the patient underwent hysterectomy. Massive cystic degeneration of a uterine leiomyoma was diagnosed histologically. Conclusion: We described the rare case of massive cystic degeneration of a uterine leiomyoma in a patient with ADPKD, in which a causal relationship was suspected. © 2015 S. Karger AG, Basel
Introduction
Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disease characterized by the formation of multiple cysts in the kidney as well as © 2015 S. Karger AG, Basel 0378–7346/15/0793–0168$39.50/0 E-Mail [email protected] www.karger.com/goi
in extrarenal organs such as the liver and pancreas [1]. The occurrence of a uterine cyst as an extrarenal manifestation of ADPKD is extremely rare. To our knowledge, only 1 case of a uterine cyst in an ADPKD patient has been reported in the English-language literature [2]. Here, we report a case of an ADPKD patient with massive cystic degeneration of a uterine leiomyoma. Case Report A 46-year-old woman was referred with a large abdominal mass, which she had noticed more than a year ago. Her periods were irregular, occurring every 30–45 days, without severe dysmenorrhea and menorrhagia. She had a history of two spontaneous abortions and had undergone dilatation and curettage at ages 38 and 39 years. She could not conceive after these abortions, but she did not consult a doctor until the present symptom occurred. Abdominal examination revealed a tense mass ranging from the lower to the upper abdomen and causing severe abdominal distension. An ultrasound examination of her abdomen revealed a cystic mass with multiple membranous structures, which were wavy in response to manipulation of the mass (fig. 1). A magnetic resonance imaging (MRI) T2weighted image showed a large and well-circumscribed high-signal mass (15.5 × 13.5 cm) located in the uterus (fig. 2). Computed tomography examination revealed a large and mostly cystic uterine mass (fig. 3a) with multiple renal and hepatic cysts (fig. 3b). The patient’s family history was remarkable for ADPKD. Her parents are married first cousins, and both parents as well as their families have a history of ADPKD. The patient’s older sister had multiple renal and hepatic cysts. A diagnosis of ADPKD with a
Takuji Tomimatsu, MD Department of Obstetrics and Gynecology Kawasaki Medical School 577, Matsushima, Kurashiki, Okayama 701-0192 (Japan) E-Mail tomimatsu @ med.kawasaki-m.ac.jp
Fig. 1. Ultrasound image of the abdomen showing a cystic mass
with multiple membranous structures.
a
Fig. 2. MRI T2-weighted image showing a large and well-circumscribed high-signal mass in the uterus.
b
Fig. 3. CT images showing a large cystic uterine mass (a) and multiple renal and hepatic cysts (b).
large uterine cyst as an extrarenal manifestation was strongly suspected. The patient was not hypertensive, and her renal function was normal at the time of referral. Although a hysterectomy was recommended to relieve her severe abdominal distension and to rule out the possibility of malignancies, the decision to perform aspiration through a small laparotomy was made because the patient opted for a fertility-sparing treatment. Following the prophylactic administration of ciprofloxacin, a second-generation fluoroquinolone, a 2-cm incision was made below the umbilicus, and a 5-mm SAND balloon catheter (Hakko Medical, Tokyo, Japan) was inserted through the uterine wall under direct visual guidance. The cyst wall was sandwiched between 2 inflated balloons, and the cyst was carefully aspirated. Because aspiration was difficult, it was stopped when 1,360 ml of serous fluid had been aspirated. Sclerotherapy was not performed in consideration of potential adverse effects on the endometrium. The operative time was 24 min, and the postoperative hospital stay was 3 days. The patient’s abdominal distension resolved after the
operation, and an abdominal ultrasound examination revealed that the uterine cyst was reduced to almost half of its previous size. Cytological analysis of the uterine cyst fluid was performed using a cell block technique as this technique has been reported to increase the sensitivity of malignancy detection and to help better demonstrate the cellular architectural pattern [3]. The aspirated fluid contained no malignant cells but only scattered histiocytes and inflammatory cells such as lymphocytes and neutrophils. A year later, the patient visited our hospital for the first time since the aspiration. We found that the uterine cyst had increased in size since the aspiration and was causing severe distension. The patient consented to total abdominal hysterectomy, and the giant uterus, weighting 3.8 kg, was removed (fig. 4a). We found a large smooth mass inside the uterine cavity (fig. 4b). The inside of the uterine mass, which contained 2,100 ml of clear serous fluid, was multilocular in nature (fig. 4c). The operative time was 109 min, blood loss was 96 ml, and the postoperative hospital stay was 7 days. Histopathological examination revealed cystic degeneration of a uterine leiomyoma.
Uterine Cyst in a Patient with ADPKD
Gynecol Obstet Invest 2015;79:168–171 DOI: 10.1159/000369996
169
b
Color version available online
a
c
Fig. 4. a Gross appearance of the uterus. b Large smooth mass inside the uterine cavity. c The inside of the uterine mass.
Discussion
ADPKD is a systemic disorder with cystic manifestations in the kidneys, liver, pancreas, seminal vesicles, and meninges [1]. Although ovarian cysts are occasionally encountered in patients with ADPKD, this association has not proved to be significant [4]. In 85–90% of cases, ADPKD results from a mutation in the PKD1 gene (polycystic kidney disease 1), which encodes polycystin-1, and in the remaining 10–15% of cases from a mutation in the PKD2 gene (polycystic kidney disease 2), which encodes polycystin-2. Both proteins are localized to the primary cilia and control the channel activity of the polycystin signaling complex, which may play a part in coordinating the cellular response to changes in extracellular fluid flow. Although the mechanisms of cyst formation in ADPKD patients remain unclear, recent evidence suggests that the dysfunction of primary cilia, called ‘ciliopathy’, plays a central role in ADPKD cystogenesis [5]. The massive uterine cyst in the present case was a manifestation of cystic degeneration of a uterine leiomyoma, which is present in up to 50% of leiomyomas, mostly in a focal form. Although the exact etiology of leiomyoma and its cystic degeneration is unknown [6, 7], diffuse cystic degeneration is extremely rare, and the largest simple cystic degenerative uterine leiomyoma reported measured 10 cm [8]. To our knowledge, this is the largest case of cystic degeneration of a uterine leiomyoma yet reported. The differential diagnosis might include cystic adenomyosis [9] or congenital Müllerian cyst [10]. Notably, the MRI findings in our case were very similar to those in a case of a giant cystic adenomyosis reported by Koga et al. [9]. 170
Gynecol Obstet Invest 2015;79:168–171 DOI: 10.1159/000369996
Percutaneous cyst aspiration and sclerosis with alcohol or minocycline under ultrasound guidance is generally performed for the treatment of renal and hepatic cysts in ADPKD patients [11]. We performed cyst aspiration through a small laparotomy using a thick catheter as we feared that uterine wall contraction and the reduction in uterine size along with cyst aspiration and the many membranous structures within the cyst might prevent complete cyst aspiration. Even so, cyst aspiration was incomplete because of aspiration difficulty, probably owing to the membranous structures inside the cyst. Cyst infection is a frequent and serious complication that often follows the aspiration of renal cysts in ADPKD patients. Therefore, uterine cyst aspiration was performed after the prophylactic administration of a fluoroquinolone, which is usually favored because the lipophilic properties of fluoroquinolone increase diffusion to the inside of the cyst. However, unlike in the case of percutaneous renal cyst aspiration, prophylactic antibiotic administration might not be needed in this case as this procedure was performed under clean and aseptic conditions. We also thought that transvaginal cyst aspiration might carry an increased risk of infection. Here, we described the rare case of massive cystic degeneration of a uterine leiomyoma in a patient with ADPKD, in which a causal relationship was strongly suspected. In ADPKD patients, every cell carries a mutated allele of either PKD1 or PKD2, which is thought to account for the systemic cyst formation characteristic of this genetic disorder. Although we do not know whether this patient had a preexisting leiomyoma, there is a possibility that the genetic mutations play a role in the cystic degeneration of such tumors. Tomimatsu/Sugihara/Nakamura/ Kashihara/Shimoya
References 1 Grantham JJ, Nair V, Winklhofer F: Cystic disease of the kidney; in Brenner BM (ed): The Kidney, ed 6. Philadelphia, WB Saunders, 2000, pp 1701–1710. 2 Okeahialam BN, Pam SD, Ekedigwe JE, Ekwempu CC: Familial polycystic kidney disease in Nigeria: a report of two cases. West Afr J Med 2006;25:249–251. 3 Thapar M1, Mishra RK, Sharma A, Goyal V, Goyal V: Critical analysis of cell block versus smear examination in effusions. J Cytol 2009; 26:60–64. 4 Heinonen PK, Vuento M, Maunola M, AlaHouhala I: Ovarian manifestations in women with autosomal dominant polycystic kidney disease. Am J Kidney Dis 2002;40:504–507.
Uterine Cyst in a Patient with ADPKD
5 Mochizuki T, Tsuchiya K, Nitta K: Autosomal dominant polycystic kidney disease: recent advances in pathogenesis and potential therapies. Clin Exp Nephrol 2013;17:317–326. 6 Shen Y, Ren ML, Xu J, Xu Q, Ding YQ, Wu ZC, Zhang HB, Huang XX, Cai YL: A multicenter case-control study on screening of single nucleotide polymorphisms in estrogenmetabolizing enzymes and susceptibility to uterine leiomyoma in Han Chinese. Gynecol Obstet Invest 2014;77:224–230. 7 Csatlós E, Rigó J Jr, Laky M, Joó JG: Gene expression patterns of insulin-like growth factor 2 in human uterine fibroid tissues: a genetic study with clinical correlations. Gynecol Obstet Invest 2013;75:185–189.
8 Yarwood RL, Arroyo E: Cystic degeneration of a uterine leiomyoma masquerading as a postmenopausal ovarian cyst. A case report. J Reprod Med 1999;44:649–652. 9 Koga K, Osuga Y, Hiroi H, Oishi H, Kugu K, Yano T, Taketani Y: Images in reproductive medicine. A case of giant cystic adenomyosis. Fertil Steril 2006;85:748–749. 10 Acién P, Acién M, Fernández F, José Mayol M, Aranda I: The cavitated accessory uterine mass: a Müllerian anomaly in women with an otherwise normal uterus. Obstet Gynecol 2010;116:1101–1109. 11 Chandok N: Polycystic liver disease: a clinical review. Ann Hepatol 2012;11:819–826.
Gynecol Obstet Invest 2015;79:168–171 DOI: 10.1159/000369996
171
Copyright: S. Karger AG, Basel 2015. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
![[Autosomal-dominant polycystic kidney disease].](/assets/img/hold.png)
