Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 332e335

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Taiwanese Journal of Obstetrics & Gynecology

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Research Letter Uterine adenosarcoma with omentum metastasis complicated by a rapidly progressing liver abscess

Hsuan-Chih Tsai a, Hsin-Yuan Lin b, Hsin-Wang Lin c, Chun-Wen Chen d, To-An Chen e, * Kuang-Hua Chen c, a Division of Family Medicine, National Defense Medical Center, Taichung Armed Force General Hospital, Taichung, Taiwan b Division of General Surgery, National Defense Medical Center, Taichung Armed Force General Hospital, Taichung, Taiwan c Division of Obstetrics and Gynecology, National Defense Medical Center, Taichung Armed Force General Hospital, Taichung, Taiwan d Division of Radiology, National Defense Medical Center, Central Taiwan University of Science and Technology, Taichung Armed Force General Hospital, Taichung, Taiwan e Division of Pathology, National Defense Medical Center, Taichung Armed Force General Hospital, Taichung, Taiwan article info

Article history: A 64-year-old married female, gravid 2, parity 2, menopaused at Accepted 21 April 2014 age 59 years. She presented to our emergency department with complaints of general malaise, abdominal pain, and heavy vaginal bleeding for 1 week. She had a history of poorly controlled type 2 diabetes mellitus (DM) and hypertensive cardiovascular disease for 2 years. After a physical examination, vital signs were uneventful, except she was febrile with a temperature of >39.8 Celsius. A large, Uterine sarcomas are a rare form of uterine malignancy that arise soft, movable mass (~10 cm in length) occupied the lower from uterine mesenchymal elements (i.e., smooth muscle and con- abdomen. There was occasional tenderness with palpation. Pelvic e nective tissue), and make up 2 5% of all uterine malignancies [1]. examination indicated a protruding mass over the cervical os. fi The Gynecologic Oncology Group classi es uterine sarcomas into Endometrial sampling was performed. The pathology report e two categories: nonepithelial and mixed epithelial nonepithelial. revealed an undifferentiated spindle cell malignancy. Ultrasound fi e Adenosarcoma is classi ed in the mixed epithelial nonepithelial examination revealed two masses and one large heterogeneous “ ”“ category and has three different subtypes: homologous, heterol- mass occupying the whole uterine cavity. Another pelvic mass, ” “ ” ogous, and adenosarcoma with high-grade stromal overgrowth. which measured 9.5 cm  7.5 cm, was connected to the enlarged The tumor often presents as a solid edematous polypoid mass uterus. Urinalysis revealed pyuria. Her serum examination was derived from the fundus. It has a low malignant potential, compared uneventful, except for elevated levels of blood sugar (335 mg/dL) to a uterine sarcoma. Adenosarcomas are often diagnosed by histo- and C-reactive protein (9.11 mg/dL). Serum levels of tumor markers logic examination. Surgery is the optimal standard treatment for such as squamous cell carcinoma antigen (SCC), alpha fetoprotein, e adenosarcoma and its recurrence [1 3]. and carcinoembryonic antigen were normal; however, the level of A pyogenic liver abscess is a common disease. The diagnosis and the tumor marker CA125 was elevated (129.9 U/mL). treatment have progressed considerably in the recent decade. Im- Abdominal CT showed a large multilobulated heterogeneous aging methods such as ultrasound (US) and multislice computed enhanced lesion that measured approximately 16.4 cm  tomography (CT) have made it possible to identify even small le- 6.1 cm  10.3 cm in the anterior lower pelvis. The tumor was sions in their initial stages. Treatment choice varies from minimally connected to the enlarged uterus (Figure 1). Another lobulated invasive procedures such as US-guided or CT-guided percutaneous heterogeneous lesion that measured approximately 4.2 cm in or laparoscopic drainage or even open drainage [4]. We report a segment 6 of liver was also present (Figure 2). The patient was rare case of uterine adenosarcoma in a patient with a rapidly admitted and diagnosed as having endometrial stromal sarcoma or developed liver abscess that mimicked tumor metastasis. The pa- uterine leiomyosarcoma with outward growth and liver metastasis. tient initially underwent a laparotomy, followed by an optimal She had a poor sugar pattern of >300 mg/dL during the few days of debulking operation 1 month later. admission. Novomix (NPH insulin 70, regular 30) (Novomix 30; Novo Nordisk Production SAS 45, Avenue d'Orle'ans, F-28002 Chartres, France) 20 units before breakfast and 10 units before * Corresponding author. Taichung Armed Force General Hospital, Division of Obstetrics and Gynecology, Number 348, Section 2, Zhongshan Road, Taiping Dis- dinner were administered after consultation with dietitians and an trict, Taichung City 411, Taiwan. endocrinology specialist. After 4 days of admission, the fever E-mail address: [email protected] (K.-H. Chen). http://dx.doi.org/10.1016/j.tjog.2014.04.029 1028-4559/Copyright © 2015, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved. H.-C. Tsai et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 332e335 333

Figure 1. Abdominal contrast-enhanced computed tomography images of (A) the coronal plane and (B) the sagittal plane shows an enlarged uterus with central soft tissue impaction in the uterine cavity (white arrow), a pedunculated myoma connected to the uterine dome (asterisk), and a multiseptated heterogeneous enhanced cystic soft tumor on the right lateral omentum (black arrow).

persisted. A repeat serum test revealed leukocytosis (i.e., white measured 11 cm  9 cm, but had measured 4.2 cm2 on the day of blood cell count, 12000/dL) and extended elevated C-reactive pro- admission) in segment 6 of the liver. Ultrasound-guided needle tein (20.9 mg/dL). Antibiotics amikacin [500 mg, intravenously (IV) aspiration was performed. The pathological report revealed daily] and cefoxitin (Lofatin; 2 gm, IV every 8 hours) were admin- extensive necrosis and abscess formation. A pelvic mass, duodenal istered after consultation with the infection specialist. For 3 days ulcer, and uterine malignancy were diagnosed and were coexistent after antibiotic treatment, she was observed for spike fevers. The with the liver abscess. The family members, general surgeon, and blood culture result was negative. Amikacin (500 mg, IV daily) and gynecologist discussed the findings with the conclusion to control cefoxitin (2 gm, IV every 8 hours) were replaced by metronidazole the duodenal ulcer and to excise the pelvic mass and liver abscess (500 mg, IV every 8 hours) and cefepime (2 gm, IV every 12 hours) first, followed by excision of the uterine malignancy. by the infection specialist on the 8th day of admission. On the 11th A laparotomy was performed with partial hepatectomy, chole- day of admission, serum examination revealed that the white cell cystectomy, and simple closure of the duodenal perforation. The count remained elevated at 16000/L and the hemoglobin level was intraoperative findings were (1) a perforated hole, which measured extremely low (5.5 g/dL). The upper gastrointestinal scope revealed 0.8 cm, over the anterior wall of the first portion of the duodenum; a giant duodenal ulcer and a gastric ulcer with bleeding. On the 11th (2) a liver abscess (12 cm  6cm 6 cm) with a honeycomb day of admission, a repeat abdominal ultrasound revealed gall appearance at liver segments 6 and 7; (3) an extrauterine tumor bladder sludge and a hypoechoic heterogeneous mass (which (13 cm  11 cm  8 cm) with a pedicle connected to the uterus; and

Figure 2. (A) The abdominal computed tomography image shows a heterogeneous contrast-enhanced lesion approximately 4.2 cm  4.2 cm in segment 6 of the liver (white arrow). (B) The repeat abdominal sonogram 11 days later, demonstrates a hypoechoic multiseptated cystic lesion over segment 6 of the liver. 334 H.-C. Tsai et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 332e335

Figure 3. (A) The laparotomy specimen from our patient demonstrates necrotic hepatic tissue filled with an abscess and a honeycomb appearance. (B) The cystic omentum tumor shows hemorrhage and focal necrosis. The pathology report reveals a high-grade sarcoma.

(4) a cystic omentum tumor (8 cm  5cm 4 cm) near the uterus tumors consist of a benign-appearing epithelial component and a (Figure 3). The histology of the extrauterine tumor was a hyalinized low-grade sarcoma. Adenosarcoma is a biphasic neoplasm leiomyoma. The cystic omentum tumor was microscopically a sar- containing an epithelium and malignant mesenchyme. Post- coma with bundles and whorls of spindle tumor cell and peripheral menopausal women have a higher risk of developing adenosarco- soft tissue involvement. mas, compared to young women. According to the current One month after the hospital admission, a total hysterectomy literature, the typical symptoms of patients with adenosarcomas and bilateral salpingo-oophorectomy were performed. The oper- are abnormal bleeding, an enlarged uterus, and tissue protruding ative findings were omental adhesions and a tumor mass with a from the external os [5]. In our patient, the presentation of ade- worm-like surface that measured 9.7 cm  6.5 cm  2.0 cm. The nosarcoma was similar to the reports. The tumor usually is a single mass protruded from the endometrium of the uterus and polypoid mass; it sometimes presents as multiple papillary masses. extended to the cervical os (Figure 4). The tumor cells micro- The tumor surface is grossly tan to brown with foci of hemorrhage scopically presented with a hypercellular mesenchymal compo- and necrosis, and occasionally has small cysts. The adenosarcoma nent composed of spindle tumor cells with focal tumor necrosis component is histopathologically a low-grade homologous stromal and hemorrhage. The patient was discharge after 3 days of sarcoma containing fibrous tissues and smooth muscle. The het- intensive care unit monitoring and 3 days of general ward care and erologous components, which consist of striated muscle, fat, and remains as an outpatient with clinic follow up. other components, are present in approximately 10e12% of tumors. Mullerian adenosarcomas are rare mixed mesenchymal and In the current literature, the heterologous elements of an adeno- epithelial neoplasms that usually arise from the uterus. These sarcoma are described as embryonal rhabdomyosarcoma and high-

Figure 4. (A) The hysterectomy specimen shows a huge gray-white polypoid tumor extending from the superficial myometrium into the uterine cavity. (B) Photomicrography shows elongated leaf-like and cleft-like glands (black arrows) composed of a single layer of cuboid epithelial cells (original magnification, Â400; hematoxylin-eosin stain). The epithelium is compressed by the hypercellular mesenchyme (white arrows). H.-C. Tsai et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 332e335 335 grade endometrial stromal cells with cartilage and differentiated Owing to the complicated coexistence of poorly controlled liver bone, respectively. Tumor nuclei are hyperchromatic with frequent abscess, pelvic mass, uterine malignancy, and perforated duodenal mitotic figures. ulcer, we first managed the life-threatening conditions (i.e., liver Adenosarcoma is often a low-grade neoplasm, compared to abscess, pelvic mass, and perforated duodenal ulcer), followed by uterine sarcomas; however, it has a recurrence rate of 25e40%. The the cytoreductive surgery of the uterine malignancy. The role of recurrence site is typically the vagina or the pelvis. Distant me- chemotherapy in the treatment of uterine adenosarcoma is unclear. tastases have been reported in 5% of patients [6]. The standard We postponed chemotherapy because of the poor comorbidities of management for adenosarcoma of the uterus is total hysterectomy our patient. We conservatively managed the patient by intense and bilateral salpingo-oophorectomy. Standard chemotherapy recurrence surveillance. One series reveals that ifosfamide plus regimens are doxorubicin, ifosfamide, trabectedin [7], or gemcita- doxorubicin with or without cisplatin, and gemcitabine plus tax- bine/docetaxel if a sarcomatous element is present [5]. There is very otere produce partial responses for adenosarcoma [6]. Even little published information on the activity and major adverse effect 3 months after discharge, our patient continued to have poor dia- of systemic therapy for uterine adenosarcoma. In our patient, the betes control. Therefore, systemic chemotherapy would have cause of the liver abscess was primarily from the bacterial trans- potentially harmed her. location of the perforated duodenal ulcer. The development of a We have presented a case of a rare uterine malignant tumor liver abscess with DM could have two causes: (1) a poor general with omentum metastasis and a rapidly progressing liver abscess, status such as DM and (2) adenosarcoma. People with DM and a which were complicated by a life-threatening perforated duodenal malignancy have a 10-fold increased risk of developing a liver ab- ulcer. We have shared our limited experience in managing this scess [8]. Adenosarcoma with sarcomatous overgrowth is a more complicated condition. aggressive disease with a higher recurrence rate. No optimal adjuvant or systemic treatment strategy has been identified; fl however, standard sarcoma chemotherapy regimens appear to be Con icts of interest efficacious in treating adenosarcoma and in treating adenosarcoma fl with sarcomatous overgrowth [6]. The authors have no con icts of interest relevant to this article. Pyogenic liver abscess (PLA) is a critical infectious disease with a high rate of morbidity and mortality. In Taiwan, the annual inci- References dence of PLA has increased from 11.2/100,000 population in 1996 to 17.6/100,000 population in 2004 [8]. Associated comorbidities that [1] Forney JP, Buschbaum HJ. Classifying staging and treating uterine sarcomas. could cause PLA include DM, pancreaticobiliary tract diseases, and Contemporary Ob Gyn 1981;18:47. 50, 55e6, 61e2, 64, 69. [2] Wickerham DL, Fisher B, Wolmark N, Bryant J, Costantino J, Bernstein L, et al. intra-abdominal infections such as cholecystitis, suppurative Association of tamoxifen and uterine sarcoma. J Clin Oncol 2002;20:2758e60. cholangitis, peritonitis, appendicitis, suppurative pylephlebitis, and [3] Major FJ, Blessing JA, Silverberg SG, Morrow CP, Creasmam WT, Currie JL, et al. diverticulitis [9e11]. Cryptogenic PLA is PLA without pan- Prognostic factors in early stage uterine sarcoma. A Gynaecologic Oncology e creaticobiliary tract disease, intra-abdominal infection, or other Group study. Cancer 1993;71:1702 9. [4] Onder A, Kapan M, Boyük€ A, Gümüs¸ M, Tekbas¸ G, Girgin S, et al. Surgical obvious etiologies. The most common causes of pyogenic abscesses management of pyogenic liver abscess. Eur Rev Med Pharmacol Sci 2011;15: are Escherichia coli, Klebsiella, and Enterococcus [11e13]. 1182e6. Mechanisms that cause PLA are an ascending infection from the [5] Clement PB, Scully RE. Mullerian adenosarcoma of the uterus: a clinicopath- ologic analysis of 100 cases with a review of the literature. Hum Pathol biliary and pancreatic ducts and hematologic spread from the or- 1990;21:363e81. gans of the portal vein system. Klebsiella pneumoniae is the most [6] Tanner EJ, Toussaint T, Leitao Jr MM, Hensley ML, Soslow RA, Gardner GJ, et al. common infectious pathogen in patients with DM who have PLA, Management of uterine adenosarcomas with and without sarcomatous overgrowth. Gynecol Oncol 2013;129:140e4. which was virtually the condition of our patient [12]. An underlying [7] Schroeder BA, Rodler ET, Loggers ET, Pollack SM, Jones RL. Clinical benefitof malignancy is an important aggravating factor of a liver abscess trabectedin in uterine adenosarcoma. Med Oncol 2013;30:501. [14]. Tumors in the hepatobiliary region may mimic an abscess and [8] Tsai FC, Huang YT, Chang LY, Wang JT. Pyogenic liver abscess as endemic disease, Taiwan. Emerg Infect Dis 2008;14:1592e600. have a grave prognosis. Pyogenic liver abscesses in patients with [9] Lederman ER, Crum NF. Pyogenic liver abscess with a focus on Klebsiella nonhepatopancreatobiliary malignant disease have a better chance pneumoniae as a primary pathogen: an emerging disease with unique clinical of a favorable outcome [15]. After a series of operations and characteristics. Am J Gastroenterol 2005;100:322e31. [10] Miedema BW, Dineen P. The diagnosis and treatment of pyogenic liver ab- intensive care unit admission, our patient had no recurrent liver scess. Ann Surg 1984;200:328e35. abscess during 6 months of follow up [15]. [11] Cohen JL, Martin FM, Rossi RL, Schoetz Jr DJ. Liver abscess. The need for In conclusion, the patient had poorly controlled DM, which complete gastrointestinal evaluation. Arch Surg 1989;124:561e4. made her more susceptible to infection by pyogenic bacteria. [12] Yang CC, Yen CH, Ho MW, Wang JH. Comparison of pyogenic liver abscess caused by non-Klebsiella pneumonia and Klebsiella pneumoniae. J Microbiol However, the final culture data failed to prove which bacteria Immunol Infect 2004;37:176e84. accounted for the rapidly progressing liver abscess, which was [13] Cheng HC, Chang WL, Chen WY, Kao AW, Chuang CH, Sheu BS. Long-term considered a PLA, based on its clinical course. The early adminis- outcome of pyogenic liver abscess: factors related with abscess recurrence. J Clin Gastroenterol 2008;42:1110e5. tration of antibiotics for the urinary tract infection probably caused [14] Lai HC, Lin CC, Cheng KS, Kao JT, Chou JW, Peng CY, et al. Increased incidence the failure in the culture results. Chemotherapy treatments are of gastrointestinal cancers among patients with pyogenic liver abscess: a unsuitable for patients with uncontrolled comorbidities. The population-based cohort study. Gastroenterology 2014;146:129e137.e1. [15] Yeh TS, Jan YY, Jeng LB, Hwang TL, Chao TC, Chien RN, et al. Pyogenic liver management of this patient included controlling the underlying abscesses in patients with malignant disease: a report of 52 cases treated at a DM by a consultation with a dietitian and endocrinology specialist. single institution. Arch Surg 1998;133:242e5.