UTERINE PAPILLARY SEROUS CARCINOMA METASTATIC TO THE CHOROID Scott D. Lawrence, MD,* Peter A. Netland, MD, PhD,* William R. Morris, MD,* Linda Smiley, MD,† Matthew W. Wilson, MD, FACS*
Purpose: To report an unusual case of choroidal metastasis from uterine papillary serous carcinoma presenting as a choroidal hemorrhage. Methods: A 70-year-old woman with a history of Stage IV endometrial cancer presented with sudden loss of vision and pain behind the right eye. Clinical examination revealed a choroidal hemorrhage with retinal detachment. The clinical findings, results of imaging studies, and pathologic findings are described. Results: The patient underwent drainage of the choroidal hemorrhage but developed a painful, blind eye resulting from secondary glaucoma that was refractory to maximal medical therapy. Examination of the drained choroidal fluid showed no malignant cells. The patient elected for enucleation of the affected eye, and histopathologic analysis was consistent with uterine papillary serous carcinoma metastatic to the choroid. The patient tolerated the procedure well. However, she entered hospice shortly after surgery to receive palliative care for her metastatic disease. Conclusion: Rare cases of uterine cancer metastasizing to the uvea have been reported. To our knowledge, this is the first case of uterine papillary serous carcinoma with uveal metastasis. Metastatic disease involving the uvea should be considered in the differential diagnosis for a patient presenting with pain and sudden loss of vision, particularly when the patient has a known primary malignancy. Histopathology and cytology can assist in identifying a uveal mass as metastatic. RETINAL CASES & BRIEF REPORTS 4:62– 64, 2010
choroid.1 Only rare cases of uterine cancer metastasizing to the uveal tract have been described. We report what we believe to be the first case of uterine papillary serous carcinoma (UPSC) with metastasis to the choroid.
From the *Department of Ophthalmology/Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis; and †West Clinic, Memphis, Tennessee.
M
etastatic uveal tumors represent the most common ocular malignancy in adults. The majority of cases arise from the breast, lung, and gastrointestinal tract with a strong predilection for the
Case Report A 70-year-old woman presented with sudden loss of vision in the right eye. She had a history of clinically stable chronic lymphocytic leukemia and Stage IV endometrial cancer treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy 4 years earlier. Lymphovascular involvement was documented at the time of diagnosis, and the patient underwent pelvic radiation and systemic chemotherapy (carboplatin and paclitaxel). Histopathology of the surgical specimen confirmed Grade 3 (poorly differentiated) UPSC, pure form. The patient received additional chemotherapy for pulmonary metastases 6 months before presentation.
Supported by unrestricted grants from Research to Prevent Blindness Inc, New York, NY, and St. Giles Foundation, New York, NY. The sponsors or funding organizations had no role in the design or conduct of this research. No proprietary interests or conflicts of interest. Reprint requests: Matthew W. Wilson, MD, FACS, Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, 930 Madison Avenue, Memphis, TN 38163; e-mail: [email protected]
62
UPSC METASTATIC TO THE CHOROID
63
Fig. 1. A, Fundus photo of the right eye reveals a large, dome-shaped lesion involving the posterior pole with associated retinal detachment. B, B-scan ultrasound showing obliteration of the vitreous by tumor centrally; choroidal fluid is noted peripherally. C, Magnetic resonance imaging (T-1 with gadolinium and fat suppression) shows a 17-mm heterogeneous mass with choroidal detachment both medially and laterally.
On examination, visual acuity was hand motions in the right eye and 20/20 in the fellow eye. Pupils were reactive with an afferent pupillary defect on the right. Slit-lamp examination revealed normal anterior segments. Intraocular pressure was 9 mmHg on the right and 16 mmHg on the left by applanation tonometry. Dilated fundus examination and imaging were consistent with a posterior segment mass and choroidal fluid (Figure 1). The differential diagnosis included uveal metastases with hemorrhage or effusion, hemorrhagic complications secondary to chemotherapy or chronic lymphocytic leukemia, and hemorrhagic choroidal malignant melanoma. Diagnostic drainage of the suprachoroidal space revealed straw-colored fluid, no neoplastic cells were found on cytology. Six days later, the patient developed severe right ocular pain. Vision was no light perception in the affected eye, and the intraocular pressure was 46 mmHg. After a minimal response to pressure-lowering agents, treatment options included retrobulbar injection (alcohol or chlorpromazine) and enucleation. The patient elected for a therapeutic and diagnostic enucleation. Histopathology on the enucleated specimen (Figure 2) demonstrated a papillary arrangement and cellular morphology consistent with the known primary neoplasm (Figure 2).
Discussion Uterine papillary serous carcinoma is a particularly aggressive form of endometrial cancer. Its propensity for extrauterine spread and distant metastases
is well documented. Prognosis is poor for those with Stage III to IV disease. Five-year survival is estimated at approximately 25%.2 A review of the literature suggests that UPSC has inherent resistance to radiotherapy3; however, recent studies suggest increased efficacy when administered in combination with chemotherapy.4 As for our patient, had her lesion been detected earlier, radiotherapy, either whole eye or brachytherapy depending on the lesion(s) size and number, would have been recommended in conjunction with her ongoing chemotherapy. The histopathology of UPSC is marked by a complex papillary structure on a fibrovascular framework. Tumor cells manifest marked atypia; nuclear pleomorphism, hyperchromasia, and macronuclei are prominent. Uterine papillary serous carcinoma may arise as a uniform tumor (pure form) or may be admixed with endometroid or clear cell variants (mixed form). These tumors can be distinguished from malignant mixed Mu¨llerian tumors, because the latter contain stromal components such as muscle, cartilage, and bone.5 Our patient’s clinical presentation was notable for its acute onset and severity of symptoms. The profound vision loss and ocular pain most likely resulted
64
RETINAL CASES & BRIEF REPORTSℜ
●
2010
●
VOLUME 4
●
NUMBER 1
Fig. 2. (Top left) Enucleated specimen showing tumor (papillary configuration) invading the choroid with a hemorrhagic component (stain, hematoxylin– eosin ⫻100, original magnification). (Bottom left) Higher magnification of the enucleated specimen reveals marked cellular atypia—nuclear pleomorphism, prominent nucleoli, and mitotic figures are evident (stain, hematoxylin–eosin ⫻400, original magnification). (Top right) Uterine papillary serous carcinoma, endometrium. Papillary configuration is similar to the metastatic lesion (stain, hematoxylin– eosin ⫻100, original magnification). (Bottom right) Higher magnification of primary tumor. Cellular morphology resembles the metastatic tumor (stain, hematoxylin– eosin ⫻400, original magnification).
from tumor growth in the choroid and a rapid-forming choroidal effusion. The development of secondary glaucoma leading to enucleation has been described as a common end point in uveal metastasis from other forms of uterine cancer.6,7 Histopathology and cytology can provide valuable information in managing a newly diagnosed uveal malignancy. First, a significant number of patients with uveal metastasis have no documented primary tumor. Timely diagnosis of the metastatic ocular lesion can guide a systemic workup aimed at identifying the primary tumor. Second, patients with one primary malignancy often develop second cancers. To assume a uveal mass to be metastatic in a patient with a known primary tumor could lead to undertreatment of an atypical primary ocular melanoma. Key words: carcinoma, choroid, hemorrhage, metastases, uterine.
References 1.
2.
3.
4.
5.
6.
7.
Shields CL, Shields JA, Gross NE, Schwartz GP, Lally SE. Survey of 520 eyes with uveal metastases. Ophthalmology 1997;104:1265–1276. Kato DT, Ferry JA, Goodman A, et al. Uterine papillary serous carcinoma (UPSC): a clinicopathologic study of 30 cases. Gynecol Oncol 1995;59:384 –389. Martin JD, Gilks B, Lim P. Papillary serous carcinoma—a less radio-sensitive subtype of endometrial cancer. Gynecol Oncol 2005;98:299 –303. Goldberg H, Miller RC, Abdah-Bortnyak R, et al. Outcome after combined modality treatment for uterine papillary serous carcinoma: a study by the Rare Cancer Network (RCN). Gynecol Oncol 2008;108:298 –305. Nicklin JL, Copeland LJ. Endometrial papillary serous carcinoma: patterns of spread and treatment. Clin Obstet Gynecol 1996;39:686 – 695. Le Rebeller J, Chauvergne J, Meuge C. A case of choroid metastasis of choriocarcinoma 关French兴. Bull Soc Ophtalmol Fr 1975;75:735–737. Spraul CW, Grossniklaus HE, Giles JT. Mullerian mixed tumor metastatic to the iris and ciliary body. Arch Ophthalmol 1997;115:122–123.
Purpose: To report an unusual case of choroidal metastasis from uterine papillary serous carcinoma presenting as a choroidal hemorrhage. Methods: A 70-year-old woman with a history of Stage IV endometrial cancer presented with sudden loss of vision and pain behind the right eye. Clinical examination revealed a choroidal hemorrhage with retinal detachment. The clinical findings, results of imaging studies, and pathologic findings are described. Results: The patient underwent drainage of the choroidal hemorrhage but developed a painful, blind eye resulting from secondary glaucoma that was refractory to maximal medical therapy. Examination of the drained choroidal fluid showed no malignant cells. The patient elected for enucleation of the affected eye, and histopathologic analysis was consistent with uterine papillary serous carcinoma metastatic to the choroid. The patient tolerated the procedure well. However, she entered hospice shortly after surgery to receive palliative care for her metastatic disease. Conclusion: Rare cases of uterine cancer metastasizing to the uvea have been reported. To our knowledge, this is the first case of uterine papillary serous carcinoma with uveal metastasis. Metastatic disease involving the uvea should be considered in the differential diagnosis for a patient presenting with pain and sudden loss of vision, particularly when the patient has a known primary malignancy. Histopathology and cytology can assist in identifying a uveal mass as metastatic. RETINAL CASES & BRIEF REPORTS 4:62– 64, 2010
choroid.1 Only rare cases of uterine cancer metastasizing to the uveal tract have been described. We report what we believe to be the first case of uterine papillary serous carcinoma (UPSC) with metastasis to the choroid.
From the *Department of Ophthalmology/Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis; and †West Clinic, Memphis, Tennessee.
M
etastatic uveal tumors represent the most common ocular malignancy in adults. The majority of cases arise from the breast, lung, and gastrointestinal tract with a strong predilection for the
Case Report A 70-year-old woman presented with sudden loss of vision in the right eye. She had a history of clinically stable chronic lymphocytic leukemia and Stage IV endometrial cancer treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy 4 years earlier. Lymphovascular involvement was documented at the time of diagnosis, and the patient underwent pelvic radiation and systemic chemotherapy (carboplatin and paclitaxel). Histopathology of the surgical specimen confirmed Grade 3 (poorly differentiated) UPSC, pure form. The patient received additional chemotherapy for pulmonary metastases 6 months before presentation.
Supported by unrestricted grants from Research to Prevent Blindness Inc, New York, NY, and St. Giles Foundation, New York, NY. The sponsors or funding organizations had no role in the design or conduct of this research. No proprietary interests or conflicts of interest. Reprint requests: Matthew W. Wilson, MD, FACS, Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, 930 Madison Avenue, Memphis, TN 38163; e-mail: [email protected]
62
UPSC METASTATIC TO THE CHOROID
63
Fig. 1. A, Fundus photo of the right eye reveals a large, dome-shaped lesion involving the posterior pole with associated retinal detachment. B, B-scan ultrasound showing obliteration of the vitreous by tumor centrally; choroidal fluid is noted peripherally. C, Magnetic resonance imaging (T-1 with gadolinium and fat suppression) shows a 17-mm heterogeneous mass with choroidal detachment both medially and laterally.
On examination, visual acuity was hand motions in the right eye and 20/20 in the fellow eye. Pupils were reactive with an afferent pupillary defect on the right. Slit-lamp examination revealed normal anterior segments. Intraocular pressure was 9 mmHg on the right and 16 mmHg on the left by applanation tonometry. Dilated fundus examination and imaging were consistent with a posterior segment mass and choroidal fluid (Figure 1). The differential diagnosis included uveal metastases with hemorrhage or effusion, hemorrhagic complications secondary to chemotherapy or chronic lymphocytic leukemia, and hemorrhagic choroidal malignant melanoma. Diagnostic drainage of the suprachoroidal space revealed straw-colored fluid, no neoplastic cells were found on cytology. Six days later, the patient developed severe right ocular pain. Vision was no light perception in the affected eye, and the intraocular pressure was 46 mmHg. After a minimal response to pressure-lowering agents, treatment options included retrobulbar injection (alcohol or chlorpromazine) and enucleation. The patient elected for a therapeutic and diagnostic enucleation. Histopathology on the enucleated specimen (Figure 2) demonstrated a papillary arrangement and cellular morphology consistent with the known primary neoplasm (Figure 2).
Discussion Uterine papillary serous carcinoma is a particularly aggressive form of endometrial cancer. Its propensity for extrauterine spread and distant metastases
is well documented. Prognosis is poor for those with Stage III to IV disease. Five-year survival is estimated at approximately 25%.2 A review of the literature suggests that UPSC has inherent resistance to radiotherapy3; however, recent studies suggest increased efficacy when administered in combination with chemotherapy.4 As for our patient, had her lesion been detected earlier, radiotherapy, either whole eye or brachytherapy depending on the lesion(s) size and number, would have been recommended in conjunction with her ongoing chemotherapy. The histopathology of UPSC is marked by a complex papillary structure on a fibrovascular framework. Tumor cells manifest marked atypia; nuclear pleomorphism, hyperchromasia, and macronuclei are prominent. Uterine papillary serous carcinoma may arise as a uniform tumor (pure form) or may be admixed with endometroid or clear cell variants (mixed form). These tumors can be distinguished from malignant mixed Mu¨llerian tumors, because the latter contain stromal components such as muscle, cartilage, and bone.5 Our patient’s clinical presentation was notable for its acute onset and severity of symptoms. The profound vision loss and ocular pain most likely resulted
64
RETINAL CASES & BRIEF REPORTSℜ
●
2010
●
VOLUME 4
●
NUMBER 1
Fig. 2. (Top left) Enucleated specimen showing tumor (papillary configuration) invading the choroid with a hemorrhagic component (stain, hematoxylin– eosin ⫻100, original magnification). (Bottom left) Higher magnification of the enucleated specimen reveals marked cellular atypia—nuclear pleomorphism, prominent nucleoli, and mitotic figures are evident (stain, hematoxylin–eosin ⫻400, original magnification). (Top right) Uterine papillary serous carcinoma, endometrium. Papillary configuration is similar to the metastatic lesion (stain, hematoxylin– eosin ⫻100, original magnification). (Bottom right) Higher magnification of primary tumor. Cellular morphology resembles the metastatic tumor (stain, hematoxylin– eosin ⫻400, original magnification).
from tumor growth in the choroid and a rapid-forming choroidal effusion. The development of secondary glaucoma leading to enucleation has been described as a common end point in uveal metastasis from other forms of uterine cancer.6,7 Histopathology and cytology can provide valuable information in managing a newly diagnosed uveal malignancy. First, a significant number of patients with uveal metastasis have no documented primary tumor. Timely diagnosis of the metastatic ocular lesion can guide a systemic workup aimed at identifying the primary tumor. Second, patients with one primary malignancy often develop second cancers. To assume a uveal mass to be metastatic in a patient with a known primary tumor could lead to undertreatment of an atypical primary ocular melanoma. Key words: carcinoma, choroid, hemorrhage, metastases, uterine.
References 1.
2.
3.
4.
5.
6.
7.
Shields CL, Shields JA, Gross NE, Schwartz GP, Lally SE. Survey of 520 eyes with uveal metastases. Ophthalmology 1997;104:1265–1276. Kato DT, Ferry JA, Goodman A, et al. Uterine papillary serous carcinoma (UPSC): a clinicopathologic study of 30 cases. Gynecol Oncol 1995;59:384 –389. Martin JD, Gilks B, Lim P. Papillary serous carcinoma—a less radio-sensitive subtype of endometrial cancer. Gynecol Oncol 2005;98:299 –303. Goldberg H, Miller RC, Abdah-Bortnyak R, et al. Outcome after combined modality treatment for uterine papillary serous carcinoma: a study by the Rare Cancer Network (RCN). Gynecol Oncol 2008;108:298 –305. Nicklin JL, Copeland LJ. Endometrial papillary serous carcinoma: patterns of spread and treatment. Clin Obstet Gynecol 1996;39:686 – 695. Le Rebeller J, Chauvergne J, Meuge C. A case of choroid metastasis of choriocarcinoma 关French兴. Bull Soc Ophtalmol Fr 1975;75:735–737. Spraul CW, Grossniklaus HE, Giles JT. Mullerian mixed tumor metastatic to the iris and ciliary body. Arch Ophthalmol 1997;115:122–123.
