DOI:10.2214/AJR.05.0004
AJR 2006; 187:99-104
© American Roentgen Ray Society
Recurrent Ovarian Cancer: Spectrum of Imaging Findings
Jin Wei Kwek1 and
Revathy B. Iyer1
1 Both authors: Department of Diagnostic Imaging, Unit 57, The University of
Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX
77030-4009.
Received January 3, 2005;
accepted after revision April 18, 2005.
Address correspondence to R. B. Iyer.
Abstract
OBJECTIVE. 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.
Keywords: cancer • genitourinary imaging • oncologic imaging • ovarian cancer
Introduction
Ovarian cancer is the second most 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].
Although 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. Autopsy
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.
After primary treatment, the patients are followed up with physical
examination, serum tumor markers such as cancer antigen (CA) 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.
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Fig. 1A —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. T2-weighted axial
unenhanced MR image of brain (A) shows heterogeneous metastasis
(long arrow) in pons with mass effect on fourth ventricle. Another
similar lesion is noted in left cerebellum (short arrow). T1-weighted
axial MR image of brain after administration of IV gadolinium (B) shows
heterogeneous enhancement in both metastatic lesions.
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Fig. 1B —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. T2-weighted axial
unenhanced MR image of brain (A) shows heterogeneous metastasis
(long arrow) in pons with mass effect on fourth ventricle. Another
similar lesion is noted in left cerebellum (short arrow). T1-weighted
axial MR image of brain after administration of IV gadolinium (B) shows
heterogeneous enhancement in both metastatic lesions.
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Fig. 2A —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.
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Fig. 2B —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. 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.
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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.
1A,
1B,
2A, and
2B). 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 (Figs.
3A and
3B). 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 (Figs. 4A and
4B) 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 (Figs.
4A and
4B), lymphangitic
carcinomatosis (Fig. 5), and
pericardial and bronchial involvement.
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Fig. 3A —52-year-old woman with stage IV recurrent ovarian carcinoma.
Axial CT section of chest shows left pleural effusion (P) and nodular pleural
thickening, consistent with pleural metastases (arrowheads).
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Fig. 4A —52-year-old woman with stage IIIC high-grade papillary serous
ovarian carcinoma with thoracic recurrence. Axial CT section of thorax shows
1.5-cm pulmonary nodule (arrow), consistent with pulmonary
metastasis.
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Fig. 4B —52-year-old woman with stage IIIC high-grade papillary serous
ovarian carcinoma with thoracic recurrence. Axial CT section through
mediastinum shows enlarged subcarinal (white arrow) and left hilar
(black arrow) nodes, compatible with metastatic adenopathy.
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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 (CA) 125 was seen during her chemotherapy. Axial CT section of
chest shows onset of lymphangitic spread in right lung (arrows), and
nodularity is noted in thickened interstitium.
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Recurrence in Solid Organs of the Abdomen
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.
3A,
3B,
6A, and
6B), 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.
3A,
3B,
6A, and
6B). 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 (Figs.
7A and
7B), adrenals, and kidneys is
rare.
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Fig. 6A —29-year-old woman with endometrioid ovarian carcinoma that
was refractory to chemotherapy after left salpingo-oophorectomy. Her cancer
antigen (CA) 125 level was rising. Baseline axial CT section shows several
ill-defined hypodense hepatic metastases (arrowheads).
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Fig. 6B —29-year-old woman with endometrioid ovarian carcinoma that
was refractory to chemotherapy after left salpingo-oophorectomy. Her cancer
antigen (CA) 125 level was rising. Follow-up CT scan shows increase in number
and size of hepatic metastases and new splenic metastasis
(arrow).
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Fig. 7A —56-year-old woman with ovarian cancer treated with
cytoreductive surgery and cisplatin-based chemotherapy 10 years earlier.
Patient presented with jaundice and pruritus. Axial CT sections show dilated
common bile duct (curved arrow, A) 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.
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Fig. 7B —56-year-old woman with ovarian cancer treated with
cytoreductive surgery and cisplatin-based chemotherapy 10 years earlier.
Patient presented with jaundice and pruritus. Axial CT sections show dilated
common bile duct (curved arrow, A) 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.
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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% (Figs. 8A
and 8B).
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Fig. 8B —47-year-old woman with recurrent papillary serous ovarian
carcinoma who presented with palpable left axillary lymphadenopathy.
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.
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Osseous and Soft-Tissue Recurrence
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Fig. 9A —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.
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Fig. 9B —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. Unenhanced (B) 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.
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Fig. 9C —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. Unenhanced (B) 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.
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Fig. 9D —44-year-old woman with recurrent papillary serous ovarian
carcinoma who presented with severe lower back pain. T1-weighted sagittal MR
image of thoracic spine shows marrow replacement (asterisk) in T2
vertebral body, in keeping with another site of bone metastasis.
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Fig. 10A —46-year-old woman with recurrent ovarian cancer treated with
chemotherapy. Axial CT scan shows soft-tissue nodule (arrow) in
subcutaneous fat of anterior abdominal wall. Surgical biopsy specimens
confirmed presence of tumor recurrence in peritoneum.
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Fig. 10B —46-year-old woman with recurrent ovarian cancer treated with
chemotherapy. CT scan shows enlarged bilateral superficial (white
arrows) and left deep (black arrow) inguinal lymph nodes,
consistent with lymph node metastases.
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Bone metastases occurred in 1.6% of patients with recurrent ovarian cancer,
the most common site of involvement being the vertebral body
[4] (Figs.
9A,
9B,
9C, and
9D). Osseous metastases may
manifest as destructive lesions on conventional radiographs; they are
associated with a soft-tissue mass on CT and MRI. Bone 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 (Figs.
10A and
10B).
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.
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Abstract
Introduction
