HISTOPATHOLOGICALLY PROVEN MUCINOUS CYSTADENOCARCINOMA METASTATIC TO THE CHOROID Robert H. Henderson, MRCOphth,* Victoria M. Cohen, FRCOphth,* Pamela P. Rath, MD,* Philip Luthert, FRCP,† John L. Hungerford, FRCOphth, FRCS*
Purpose: To report the first case of conventional transcleral choroidal biopsy in the diagnosis of ovarian carcinoma metastatic to the choroid and to summarize the published cases of ovarian carcinoma metastatic to the choroid. Methods: Case report and Medline literature review. Results: This is the tenth case reported in the literature and the only case that underwent conventional transcleral choroidal biopsy. Transcleral choroidal biopsy allowed the diagnosis of metastatic mucinous cystadenocarcinoma of the ovary. Choroidal metastases are not associated with central nervous system involvement; however, investigations may reveal distal boney or pulmonary metastases. Conclusion: Ovarian carcinoma rarely metastases to the choroid and unlike breast carcinoma, concurrent central nervous system disease has not been reported. When systemic investigations fail to reveal active intraperitoneal disease or distal metastases, the clinician should consider referral to an ocular oncology center for a choroidal biopsy. RETINAL CASES & BRIEF REPORTS 4:181–183, 2010
From the *Ocular Oncology Service, Moorfields Eye Hospital, London, UK; and †The Institute of Ophthalmology, London. UK.
pigment clumping was present (Figure 1). B-scan ultrasonography revealed a mass measuring 12.8 ⫻ 10.6 mm in base and 3.3 mm in height. The mass demonstrated acoustic solidarity suggestive of a choroidal metastasis. Systemic investigations, including mammography, chest radiograph, and abdominal computed tomography scan, failed to reveal a primary carcinoma or disseminated metastases. Normal C125 and imaging of the pelvis ruled out recurrence of her ovarian carcinoma. A transcleral choroidal biopsy was performed to determine the nature of the lesion. The tumor was approached from the superior temporal quadrant and identified with scleral indentation. A partial-thickness scleral flap was created and full-thickness sclerotomy revealed an avascular gelatinous choroidal mass. Despite the posterior location of the lesion, no complications were encountered. Histopathology showed nodules of malignant epithelial cells with large cytoplasmic vacuoles and mucinous cytoplasm (Figure 2). Moderate nuclear pleomorphism and mitoses were iden-
50-year-old woman presented to her referring ophthalmologist with a scotoma below fixation. One year previously, she was diagnosed with Stage Ic moderately differentiated mucinous cystadenocarcinoma of the ovary. She underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, distal omentectomy, and six cycles of adjuvant carboplatin. The patient was referred to the ocular oncology service with visual acuity of 6/60 on the right and 6/6 on the left. Examination of the right posterior pole led to the discovery of an elevated pale subretinal mass at the macular abutting the optic nerve. The lesion had a mottled diffuse appearance and Reprint requests: Victoria M. Cohen, FRCOphth, Consultant Ocular Oncologist, Moorfields Eye Hospital, City Road, London EC1V 2PD, UK; e-mail: [email protected]
RETINAL CASES & BRIEF REPORTSℜ
Fig. 1. Photography of the right fundus at presentation. A symptomatic, isolated, pale choroidal mass with overlying pigment clumping was seen at the posterior pole.
tified. The appearances were consistent with metastatic mucinous cystadenocarcinoma from an ovarian primary tumor, reclassified as Stage IV. She underwent external beam radiotherapy to the eye. Within a few months of her ocular diagnosis, multiple bony metastases and bilateral malignant pleural effusions were discovered. Despite further chemotherapy, she sustained cardiac failure secondary to underlying malignancy and died 18 months later. Comment Epithelial ovarian tumors account for 85% to 95% of all ovarian cancers. They may be mucinous
Fig. 2. Light microscopy of the right choroidal biopsy specimen. High magnification of choroidal metastases showing features of metastatic mucinous cystadenocarcinoma (hematoxylin– eosin-stained section, original magnification ⫻1000).
(most common) or serous cystadenocarcinoma, endometrial, undifferenciated, or clear cell. Ovarian cancers disseminate primarily by continuity and lymphatic dissemination to the pelvis, para-aortic lymph nodes, and peritoneum is common. Hematogenous dissemination results in distal metastases (Stage IV disease), although the site of metastases is not related to the histology or grading of the tumor. Central nervous system involvement is rare, comprising 0.9% of distant metastases from the ovary. However, the frequency of choroidal metastases in ovarian carcinoma is unknown.1 Breast cancer is the most common primary tumor to metastasize to the choroid and ovarian cancer is associated with breast cancer through BRCA1 and 2 genetic mutations. Therefore, patients with choroidal metastases and a history of ovarian cancer should still undergo mammography to rule out metastases from a second primary tumor. Because improved chemotherapy allows for longer patient survival, the previously rare distal sites of metastases may become more common.2,3 This is the tenth case of choroidal metastasis from ovarian carcinoma reported and therefore creates an opportunity to review the literature (Table 1). There is only one report in which ocular metastases predate the discovery of the primary ovarian tumor.4 In our case and all other reports,2,3,5–10 there was a history of ovarian carcinoma. Choroidal metastases from ovarian carcinoma were not associated with central nervous system metastases (Table 1). Distal metastases with or without intraperitoneal relapse were present in 6 of 10 published cases (Table 1), thus emphasizing the value of systemic investigations for presumed ovarian malignancy metastatic to the choroid. In this patient and the case reported by Heerma and Sudilovsky,9 the choroid was the first distal site involved; subsequent follow-up revealed widespread distal metastases. A choroidal biopsy should be considered if no other distal metastases, accessible for biopsy, are identified. Heerema and Sudilovsky9 used fine needle aspiration biopsy to reveal the diagnosis of ovarian mucinous cystadenocarcinoma metastatic to the choroid. A conventional transcleral approach was adopted in our patient because the tumor was only 3.3 mm high and the surgeon was concerned that fine needle aspiration biopsy may not provide sufficient material for diagnosis. In addition, the histopathological diagnosis was more likely to be accurate with a solid specimen rather than a cell aspirate. The biopsy was uncomplicated and allowed the diagnosis of mucinous cystadenocarcinoma metastatic to the choroid. After the diagnosis of distal metastasis in ovarian carcinoma, the outlook for survival is poor. The mean
MUCINOUS CYSTADENOCARCINOMA TO THE CHOROID Table 1. Ovarian Cystadenocarcinoma Metastatic to the Choroid: A Summary of the Published Cases Associated Distal Metastases
Histology of Primary Ovarian Cancer Hauksson5 Grendys10 White6 Kushner7 Patsner2 Krohn-Hansen4 Akahira8 Heerema9 Kim3 Current report 2009
Serous cystadenocarcinoma Serous cystadenocarcinoma Mucinous cystadenocarcinoma Serous cystadenocarcinoma Clear cell carcinoma Mucinous cystadenocarcinoma Mucinous cystadenocarcinoma Mucinous cystadenocarcinoma Mucinous cystadenocarcinoma Mucinous cystadenocarcinoma
Survival in Months Lung Active After Discovery of and/or Intraperitoneal Choroidal CNS Bone Disease Metastases
Histology-Proven Choroidal Metastastes No No No
No No No
Yes No No
Yes Yes No
4 16 N/A
No No Yes, autopsy
No No No
No No Yes
No Yes Yes
N/A 36 5
Yes, transcleral biospy
CNS, central nervous system; N/A, not available; FNAB, fine needle aspiration biopsy.
survival after the diagnosis of choroidal metastases is 12 months (range, 1.5–36 months) (Table 1). Therefore, patients should receive external beam radiotherapy to rapidly shrink the metastases, resolve subretinal fluid, and restore vision, therein improving the patient’s quality of life. Radiotherapy complications are unlikely to affect these patients during their lifetime. Chemotherapy is required if other organs are involved; however, in our experience, chemotherapy alone is unsuccessful in the rapid regression of choroidal metastases. In conclusion, ovarian carcinoma metastatic to the choroid is not associated with central nervous system metastases and has a poor prognosis. If systemic investigations fail to reveal other distal metastases or active intraperitoneal disease, a choroidal biopsy should be considered to ascertain the diagnosis. Conventional transcleral choroidal biopsy is a challenging procedure that should be undertaken in a specialist ocular oncology center. Key words: choroid, radiotherapy, metastasis, ovarian cystadenocarcinoma, transcleral biopsy.
Cohen ZR, Suki D, Weinberg JS, et al. Brain metastases in patients with ovarian carcinoma: prognostic factors and outcome. J Neurooncol 2004;66:313–325.
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