Recurrent Ovarian Cancer Women s Imaging Pictorial Essay Downloaded from www.ajronline.org by 80.243.130.157 on 03/08/18 from IP address 80.243.130.157. Copyright RRS. For personal use only; all rights reserved WOMEN S IMGING Jin Wei Kwek 1 Revathy. Iyer Kwek JW, Iyer R Keywords: cancer, genitourinary imaging, oncologic imaging, ovarian cancer DOI:10.2214/JR.05.0004 Received January 3, 2005; accepted after revision pril 18, 2005. 1 oth authors: Department of Diagnostic Imaging, Unit 57, The University of Texas M. D. nderson Cancer Center, 1515 Holcombe lvd., Houston, TX 77030-4009. ddress correspondence to R.. Iyer. JR 2006; 187:99 104 0361 803X/06/1871 99 merican Roentgen Ray Society Recurrent Ovarian Cancer: Spectrum of Imaging Findings OJECTIVE. The purpose of this article is to show the appearance of atypical sites of metastasis in patients with recurrent ovarian cancer. CONCLUSION. Metastatic disease from ovarian cancer outside of the peritoneal cavity is generally rare at presentation but is increasingly seen in patients who have recurrent disease, despite multiple therapies. It is important for radiologists to recognize atypical sites of metastasis in patients with recurrent ovarian cancer to facilitate earlier diagnosis and treatment. varian cancer is the second most O common gynecologic malignancy and the most common cause of death in women with gynecologic malignancies [1]. Most women diagnosed with ovarian cancer and treated with debulking surgery and adjuvant chemotherapy will ultimately relapse. Metastases outside of the peritoneal cavity and abdominopelvic lymph nodes are rare at presentation but are increasingly recognized during treatment [2]. This may be because of improving imaging techniques and because the therapy is increasingly successful at controlling peritoneal disease, so that patients live longer and show manifestations of distant disease that would not otherwise have become evident. It is important for radiologists to recognize the unusual sites of recurrent ovarian cancer because such knowledge will facilitate early diagnosis and prompt treatment. Routes of Spread Intraperitoneal dissemination is commonly seen, and disease usually remains confined to the peritoneal cavity at presentation. Ovarian cancer may also spread through lymphatic channels. The most common pathway of lymphatic spread follows the ovarian vessels to retroperitoneal nodes near the renal hila. The second pathway passes laterally in the broad ligament to the internal iliac and obturator nodes along the pelvic sidewall. The third group passes with the round ligament to the external iliac and inguinal nodes. Extraabdominal nodal metastases are rare at presentation but do occur in recurrent disease. Hematogenous spread occurs late during the course of the disease and is more commonly associated with recurrence than with presentation of disease [2 4]. The most common sites of metastases are the pleural cavity, liver, and lung. Sites of parenchymal metastases are similar to those of other carcinomas. The presence of lymphatic and vascular invasion in the primary tumor is predictive of such involvement [5]. lthough most ovarian cancers spread according to the patterns just described, certain tumors may have a predilection for a particular route. For example, dysgerminoma spreads to lymph nodes more commonly, whereas choriocarcinoma predominantly spreads by the hematogenous route. utopsy studies have shown that approximately 50% of distant metastases are asymptomatic, so the true incidence of distant dissemination is probably even higher than reported in clinical series [4]. Treatment and Follow-Up of Ovarian Cancer Primary cytoreductive surgery followed by systemic cisplatin-based chemotherapy is the usual therapeutic option for primary ovarian cancers. fter primary treatment, the patients are followed up with physical examination, serum tumor markers such as cancer antigen (C) 125, imaging, or second-look surgery. CT and MRI are the traditional imaging techniques for surveillance and both have fairly similar accuracy. CT is performed most often because of its availability. PET/CT combines functional and anatomic imaging and may increase diagnostic confidence for the detection of recurrent disease. JR:187, July 2006 99
Downloaded from www.ajronline.org by 80.243.130.157 on 03/08/18 from IP address 80.243.130.157. Copyright RRS. For personal use only; all rights reserved Fig. 1 58-year-old woman treated with tumor reductive surgery and chemotherapy for stage IV papillary serous adenocarcinoma of the ovary. Patient showed good initial response to chemotherapy, with reduction in size of residual tumor and hepatic metastases. She presented with dizziness and left-sided weakness 1 year after initial diagnosis. and, T2-weighted axial unenhanced MR image of brain () shows heterogeneous metastasis (long arrow) in pons with mass effect on fourth ventricle. nother similar lesion is noted in left cerebellum (short arrow). T1- weighted axial MR image of brain after administration of IV gadolinium () shows heterogeneous enhancement in both metastatic lesions. Fig. 2 68-year-old woman with stage IIIC high-grade papillary serous adenocarcinoma of the ovary treated with cytoreductive surgery and six cycles of carboplatin and paclitaxel. Patient presented 4 years after initial diagnosis with focal jerking of right arm and leg that progressed to a generalized seizure and loss of consciousness for 30 min., T2-weighted axial MR image of brain shows heterogeneous mass (arrow) in right temporal lobe and surrounding edema., T1-weighted axial MR image of brain after administration of IV gadolinium shows heterogeneously enhancing metastasis (arrow). Patient underwent right temporal craniotomy and excision of tumor. Histology was consistent with poorly differentiated metastatic adenocarcinoma. The usual manifestations of recurrent ovarian cancers are pelvic masses in the surgical bed, peritoneal carcinomatosis, retroperitoneal lymph node metastases, pleuropulmonary metastases, and hepatic metastases. Recurrences in extrahepatic solid organs of the abdomen, the CNS, bone, and subcutaneous fat or muscle do occur and are increasingly recognized. Patients who received cisplatin as part of their initial treatment regimen have been reported to have a higher incidence of metastases to the adrenal glands, thoracic nodes, bladder, and liver that were not explained by differences in survival [6]. Recurrence in the CNS Cerebral metastases in epithelial ovarian carcinoma generally occur late in the course of disease, but the incidence is increasing, occurring in patients with a prolonged survival caused by repeated chemosensitive relapses [7] (Figs. 1 and 2). The overall frequency of brain metastasis found at autopsy is reported to be about 6% [5]. The median time for CNS relapse was 46 months in one series, compared with 6 months for hematogenous spread to other sites such as liver and lungs [7]. The brain may be a sanctuary site from systemic chemotherapy because of the blood brain barrier, and long-term survival permits occult CNS metastases to become overt. Isolated cases of leptomeningeal metastases have been reported [8]. Recurrence in the Thorax Pleural effusion is the most common manifestation of thoracic involvement at imaging. The presence of pleural thickening and nodules in association with pleural effusion is diagnostic of pleural metastases (Fig. 3). Thoracentesis yielding malignant cells is required for diagnosis of malignant effusion in the absence of pleural nodules or thickening on CT. The reported incidence of metastatic pulmonary nodules (Fig. 4) ranges from 34% to 38% in all patients with recurrent disease, and most of these are asymptomatic [3, 5]. The frequency of pleural disease at autopsy is approximately 25% [5]. Other less common manifestations include mediastinal lymphadenopathy (Fig. 4), lymphangitic carcinomatosis (Fig. 5), and pericardial and bronchial involvement. 100 JR:187, July 2006
Recurrent Ovarian Cancer Downloaded from www.ajronline.org by 80.243.130.157 on 03/08/18 from IP address 80.243.130.157. Copyright RRS. For personal use only; all rights reserved Fig. 3 52-year-old woman with stage IV recurrent ovarian carcinoma., xial CT section of chest shows left pleural effusion (P) and nodular pleural thickening, consistent with pleural metastases (arrowheads)., CT scan also shows hepatic (black arrow) and splenic (white arrows) metastases. Fig. 4 52-year-old woman with stage IIIC high-grade papillary serous ovarian carcinoma with thoracic recurrence., xial CT section of thorax shows 1.5-cm pulmonary nodule (arrow), consistent with pulmonary metastasis., xial CT section through mediastinum shows enlarged subcarinal (white arrow) and left hilar (black arrow) nodes, compatible with metastatic adenopathy. Fig. 5 48-year-old woman with stage IIIC clear cell carcinoma of the ovary who was receiving chemotherapy after surgery. Dramatic increase of cancer antigen (C) 125 was seen during her chemotherapy. xial CT section of chest shows onset of lymphangitic spread in right lung (arrows), and nodularity is noted in thickened interstitium. JR:187, July 2006 101
Downloaded from www.ajronline.org by 80.243.130.157 on 03/08/18 from IP address 80.243.130.157. Copyright RRS. For personal use only; all rights reserved Recurrence in Solid Organs of the bdomen Hematogenous dissemination to the abdominal organs may occur in patients with recurrent disease. The liver is the most common site of solid organ metastases in the abdomen (Figs. 3 and 6), with a reported incidence of 45 48% at autopsy [3, 5], followed by the spleen with a reported frequency of 15% at autopsy [2, 5] (Figs. 3 and 6). Isolated splenic metastasis can occur with ovarian cancer, unlike gastrointestinal tumors, although the spleen is still a rare site for recurrent ovarian cancer. The presence of calcifications in metastatic lesions is common in mucinous tumors. Involvement of the pancreas (Fig. 7), adrenals, and kidneys is rare. Distant Lymph Node Recurrence The prevalence of distant lymph node recurrence beyond the pelvic and paraaortic chains in the setting of recurrent ovarian carcinoma has been reported to be 7.1% (Fig. 8). Fig. 6 29-year-old woman with endometrioid ovarian carcinoma that was refractory to chemotherapy after left salpingo-oophorectomy. Her cancer antigen (C) 125 level was rising., aseline axial CT section shows several ill-defined hypodense hepatic metastases (arrowheads)., Follow-up CT scan shows increase in number and size of hepatic metastases and new splenic metastasis (arrow). Fig. 7 56-year-old woman with ovarian cancer treated with cytoreductive surgery and cisplatin-based chemotherapy 10 years earlier. Patient presented with jaundice and pruritus. and, xial CT sections show dilated common bile duct (curved arrow, ) caused by obstruction by ill-defined hypodense mass (straight arrow) in pancreatic head. Patient underwent exploratory laparotomy and biopsy of mass in pancreatic head. Histology was consistent with poorly differentiated metastatic carcinoma of ovarian origin. Incidentally, she had chronic right hydronephrosis (K) related to congenital ureteropelvic junction obstruction and marked thinning of renal parenchyma. 102 JR:187, July 2006
Recurrent Ovarian Cancer Fig. 8 47-year-old woman with recurrent papillary serous ovarian carcinoma who presented with palpable left axillary lymphadenopathy., CT scan of chest shows left axillary node (L)., Longitudinal sonogram obtained during fine-needle aspiration biopsy shows enlarged hypoechoic left axillary lymph node and loss of fatty hilum that proved to be metastatic ovarian carcinoma. Downloaded from www.ajronline.org by 80.243.130.157 on 03/08/18 from IP address 80.243.130.157. Copyright RRS. For personal use only; all rights reserved C Fig. 9 44-year-old woman with recurrent papillary serous ovarian carcinoma who presented with severe lower back pain. High T1 signal anterior to the spine is compatible with prevertebral fat., Lateral lumbar radiograph shows collapsed L3 vertebra. and C, Unenhanced () and gadolinium-enhanced (C) sagittal Tl-weighted MR images of lumbar spine show collapsed L3 vertebra with enhancement (arrow) and retropulsion of bone fragment into spinal canal. CT-guided fine-needle aspiration biopsy showed evidence of bone metastasis. (Fig. 9 continues on next page) JR:187, July 2006 103
Downloaded from www.ajronline.org by 80.243.130.157 on 03/08/18 from IP address 80.243.130.157. Copyright RRS. For personal use only; all rights reserved Fig. 9 (continued) 44-year-old woman with recurrent papillary serous ovarian carcinoma who presented with severe lower back pain. D, T1-weighted sagittal MR image of thoracic spine shows marrow replacement (asterisk) in T2 vertebral body, in keeping with another site of bone metastasis. Osseous and Soft-Tissue Recurrence one metastases occurred in 1.6% of patients with recurrent ovarian cancer, the most common site of involvement being the vertebral body [4] (Fig. 9). Osseous metastases may manifest as destructive lesions on conventional radiographs; they are associated with a soft-tissue mass on CT and MRI. one scans and PET/CT show increased activity at sites of osseous metastases. Other rare sites of reported recurrences include the skin and subcutaneous tissues, the thymus, the thyroid, the breast, and the urinary tract [2 4]. Of these, metastases to the subcutaneous tissue are probably the most frequent, with a reported incidence of 3.5% [4]. They manifest as discrete enhancing nodules or masses in the subcutaneous fat (Fig. 10). D Summary Unusual sites of ovarian cancer recurrences are increasingly recognized in clinical practice because of advances in chemotherapy and radiation therapy and longer patient survival, and because of the manifestation of distant metastases that may otherwise not occur or be clinically silent. Radiologists should be aware of this changing pattern of disease spread in ovarian cancer patients who receive aggressive chemotherapy or radiation therapy. References 1. Jemal, Tiwari RC, Murray T, et al. Cancer statistics, 2004. C Cancer J Clin 2004; 54:8 29 2. Cormio G, Rossi C, Cazzolla, et al. Distant metastases in ovarian carcinoma. Int J Gynecol Cancer 2003; 13:125 129 3. Rose PG, Piver MS, Tsukada Y, Lau TS. Metastatic Fig. 10 46-year-old woman with recurrent ovarian cancer treated with chemotherapy., xial CT scan shows soft-tissue nodule (arrow) in subcutaneous fat of anterior abdominal wall. Surgical biopsy specimens confirmed presence of tumor recurrence in peritoneum., CT scan shows enlarged bilateral superficial (white arrows) and left deep (black arrow) inguinal lymph nodes, consistent with lymph node metastases. patterns in histologic variants of ovarian cancer: an autopsy study. Cancer 1989; 64:1508 1513 4. Dauplat J, Hacker NF, Nieberg RK, erek JS, Rose TP, Sagae S. Distant metastases in epithelial ovarian carcinoma. Cancer 1987; 60:1561 1566 5. Dvoretsky PM, Richards K, ngel C, et al. Distribution of disease at autopsy in 100 women with ovarian cancer. Hum Pathol 1988; 19:57 63 6. Reed E, Zerbe CS, rawley OW, icher, Steinberg SM. nalysis of autopsy evaluations of ovarian cancer patients treated at the National Cancer Institute, 1972 1988. m J Clin Oncol 2000; 23:107 116 7. Kolomainen DF, Larkin JM, adran M, et al. Epithelial ovarian cancer metastasizing to the brain: a late manifestation of the disease with an increasing incidence. J Clin Oncol 2002; 20:982 986 8. Park CM, Kim SH, Moon MH, Kim KW, Choi HJ. Recurrent ovarian malignancy: patterns and spectrum of imaging findings. bdom Imaging 2003; 28:404 415 104 JR:187, July 2006