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OVARIAN CANCER WITH INITIAL SYMPTOM OF PULMONARY EMBOLISM: A CASE REPORTJung-Woo Park, MD, Sung-Ook Hwang, MD, Byoung-Ick Lee, MD, Jee-Hyun Park, MD, Jeong-Hoon Lee, MD, Eunseop Song, MDDepartments of Obstetrics and Gynecology, Inha University College of Medicine, Incheon, Korea

Venous thromboembolism often occurs after major surgery and may occur as a consequence of underlying cancer. A 39-year-old woman presented to the emergency room with chief complaints of dyspnea and right chest pain. Chest computed tomography (CT) revealed pulmonary artery thromboembolism of the left lobe and a massive right pleural effusion. D-dimer level was 40.4 µg/mL. Abdomino-pelvic CT revealed a 15×12×14 cm solid and cystic mass in the pelvic cavity, suggesting ovarian cancer. A pleural biopsy found metastatic adenocarcinoma. She underwent cytoreductive surgery and pathologic findings revealed malignant mullerian mixed tumor of ovary. The hypercoagulable state in patients with ovarian cancer may occur as an initial symptom of pulmonary embolism. It is unresponsive to standard anticoagulation therapy. The hypercoagulable state in patient with ovarian cancer may be stopped by cytoreductive surgery of the malignancy.

Keywords: Ovarian cancer; Pulmonary embolism; Venous thromboembolism

Received: 2012.5.11. Revised: 2012.6.12. Accepted: 2012.7.3.Corresponding author: Eunseop Song, MDDepartment of Obstetrics and Gynecology, Inha University College of Medicine, 27 Inhang-ro, Jung-gu, Incheon 400-711, KoreaTel: +82-32-890-3430 Fax: +82-32-890-3097E-mail: songsong2000@hotmail.com

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Copyright © 2012. Korean Society of Obstetrics and Gynecology

The association between venous thrombosis and malignancy was first described by Trousseau [1] in 1865 and this has been con-firmed by several clinical, pathologic and laboratory studies. The thromboembolic event occurs before the diagnosis of cancer, and it has an increased risk of ovarian cancer during the first year of follow-up [2]. A previous report suggests that venous thrombo-embolism (VTE) may occur as a consequence of underlying cancer, and VTE can be detected prior to the diagnosis of cancer. Some authors estimate that as many as 15% of patients with ovarian cancer will have a thromboembolism [3]. A study on incidental pulmonary embolism (PE) in patients with cancer revealed that the highest prevalence occurred in patients with gynecologic malig-nancies [4].We report a case of a 39-year-old patient with ovarian cancer and PE as the initial symptom.

Case Report

A 39-year-old woman presented to the emergency room with the chief complaints of dyspnea and right chest pain that had begun a few days earlier. She was healthy at birth and had no past history

of underlying disease or clotting abnormality. There was no history of oral medication, pregnancy, or any other gynecological/surgical problem. On presentation, she was mild febrile, had tachycardia with a regular rate, and her lungs were clear on auscultation. Laboratory studies revealed a hemoglobin value of 10.9 g/dL; prothrombin time 16.5 sec (normal range [NR], 11.0 to 15.0 sec); partial thromboplastin time 45.0 sec (NR, 29.0 to 44.0 sec); D-dimer 40.4 µg/mL (NR<0.4 µg/mL); and C-reactive protein (CRP) 11.53 mg/dL (NR<0.3 mg/dL).

CASE REPORTKorean J Obstet Gynecol 2012;55(8):606-609http://dx.doi.org/10.5468/KJOG.2012.55.8.606pISSN 2233-5188 · eISSN 2233-5196

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Jung-Woo Park, et al. Ovarian cancer with pulmonary embolism

Chest CT revealed pulmonary artery thromboembolism of the left lobe and a massive right pleural effusion (Fig. 1). Abdomino-pelvic CT revealed a 15 ×12 ×14 cm solid and cystic mass in the pelvic cavity suggesting ovarian cancer (Fig. 2A) and a wedge-shaped low attenuated lesion in the mid-pole of the left kidney suggesting kidney infarction (Fig. 2B). A cytological examination of the pleural effusion and pleural biopsy revealed metastatic adenocarcinoma. The serum CA-125 level was 768.0 U/mL (NR<35.0 U/mL). Based

on these findings; she was diagnosed with ovarian cancer with PE and kidney infarction. Unfractionated heparin (10,000 U/day) was administered as perioperative anticoagulant treatment.She underwent cytoreductive surgery including total abdominal hysterectomy and bilateral salpingo-oophorectomy. The pathologi-cal findings revealed a malignant mullerian mixed tumor of the ovary. After the operation, she complained of swelling and weak-ness of the left leg. 3D-Angio CT of the lower extremity revealed deep vein thrombosis in the bilateral popliteal and calf veins. An infrarenal inferior vena cava filter was inserted. Brain MR Angi-ography revealed total obstruction of the right proximal middle

Fig. 1. Enhanced computed tomography scan of chest showing pulmo-nary embolism (arrow) and massive right pleural effusion.

Fig. 2. Abdomino-pelvic computed tomography showed solid and cystic mass in pelvic cavity (A), and wedge shaped low attenuated lesion in mid pole of left kidney (B).

A B

Fig. 3. Brain magnetic resonance angiography showed total obstruction of right proximal middle cerebral artery (arrow).

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cerebral artery (Fig. 3). Trans-esophageal echocardiogram dem-onstrated some vegetation and mobile echodensity on the atrial surface of the mitral valve (Fig. 4). Infectious endocarditis was suspected with brain infarctions and deep vein thrombosis thus empiric therapy with intravenous antibiotics was initiated. Despite persistent fever and leukocytosis, serial blood cultures remained sterile. Nonbacterial thrombotic endocarditis (NBTE) was sus-pected. The patient received six cycles of postoperative adjuvant therapy with carboplatin and paclitaxel. Follow-up echocardio-grams have shown a gradual regression in the size and the extent of the vegetations. However, her metastatic lung lesion worsened and she died 14 months after her initial visit.

Discussion

PE as a paraneoplastic feature can be caused by a wide range of malignancies (e.g., those of the pancreas, lung, stomach, liver and ovary). Malignancy is generally associated with a hyperco-agulable state [5]. PE and venous thromboses are complications due to a hypercoagulable state. Both the stenosis of the iliac vein as a result of compression by the ovarian tumor and the presence of ovarian cancer may have been involved in our patient’s deep venous thrombosis (DVT). In fact, the association between can-cer and DVT is well known, and PE secondary to DVT caused by compression of the pelvic venous system has been reported [6]. However, large tumors or massive ascites in ovarian cancer may compress the intrapelvic veins and increase the risk of DVT even before surgery. For prevention of DVT after surgery, we usually use elastic stockings during surgery and intermittent pneumatic

compression during and after surgery. However, if the DVT exists before treatment of ovarian cancer, such preventative measures may be ineffective or possibly dangerous for lethal PE.Acute VTE can be the first manifestation of an occult malignancy, and patients presenting with idiopathic VTE are more likely to have underlying cancer than those patients in whom a secondary cause of thrombosis is apparent. Based on a prospective medical database of a county population in the United States, a rough es-timate of the annual incidence of VTE in a cancer population is ap-proximately 1/200 [3]. About 10% of the patients with idiopathic VTE were diagnosed with subsequent cancers over the next 5 to 10 years, and the diagnosis is established within the first year of presentation of DVT in over 75% of cases [7,8].Ovarian cancer of our patient was asymptomatic and was diag-nosed during the examination of PE. To our knowledge, PE as the initial symptom is rare in patients with ovarian cancer. A study of cerebral infarction associated with ovarian cancer has identified the main cause as NBTE or hypercoagulability [9]. The hypercoagulable state in patients with ovarian cancer cannot be influenced by standard anticoagulation therapy with heparin or coumadin derivatives, but it has been reported to be stopped by curative resection of the tumor, avoiding an extremely poor out-come [10,11]. Treatment of the hypercoagulable state itself does not have a great influence on prognosis; successful treatment of the primary disease is said to most influence the prognosis. Lim et al. reported that extensive cytoreductive effort is important not only to minimize residual tumor growth but also to decrease post-operative VET [12].We experienced an ovarian cancer patient with the initial symp-tom of PE and kidney infarction who had cerebral infarction post-operatively. The hypercoagulable state in patients with ovarian cancer may occur as an initial symptom of PE. It is unresponsive to standard anticoagulation therapy. The hypercoagulable state in patient with ovarian cancer may be stopped by cytoreductive sur-gery of the malignancy.

Acknowledgements

This work was supported by INHA University Research Grant.

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난소암에서 초기증상으로 발생한 폐색전증 1예

인하대학교 의과대학 산부인과학교실

박정우, 황성욱, 이병익, 박지현, 이정훈, 송은섭

정맥혈전색전증은 암과 연관되고 암수술 후에 발생빈도가 높다. 호흡곤란과 우측 가슴통증을 주소로 내원한 39세 여환이 응급실에 내원

하였다. 흉부단층촬영 소견상에서 좌측 폐에 폐색전증의 소견과 우측 폐에 흉수의 소견이 있었다. D-dimer 40.4 µg/mL였고, 복부단층촬

영 소견상에서는 난소암으로 의심되는 종양이 발견되었다. 흉막 조직검사상에서 전이성 선암 소견이 나왔으며, 환자는 종양감축수술을 시

행받고 병리 소견상 악성 혼합뮐러종양으로 판명되었다. 난소암에서의 초기 증상으로 폐색전증은 환자의 응고항진상태와 연관이 있으며,

통상적인 항응고제 치료로는 효과가 적다. 이런 응고항진상태는 암의 근원적 종양감축수술에 의해 치료될 수 있다.

중심단어: 난소암, 폐색전증, 정맥혈전색전증