Intracranial metastases from prostate adenocarcinoma are very unusual, and initial presentation with symptomatic brain involvement is especially rare. We describe a 65-year-old male who presented with blurred vision and was found to have abducent nerve involvement and high-grade metastatic prostate cancer. Computed tomography of his head revealed a destructive lesion involving the clivus. He was started on hormonal treatment and his visual symptoms improved. Repeat scans after 6 months revealed resolution of the clivus lesion. Prostate cancer can occasionally present with neurologic manifestations, predominantly due to metastatic involvement of the skull bone. Awareness of this possibility could lead to accurate diagnosis. Initiation of appropriate therapy can successfully reverse the neurologic deficits.
Ashish Bhargava,1 Hussein Aoun,2 Mehsati Herawi,3 Ulka Vaishampayan1
1 Department of Internal Medicine, Wayne State University, Karmanos Cancer Institute, Detroit Michigan, USA
2Department of Radiology, Wayne State University, Karmanos Cancer Institute, Detroit Michigan, USA
3 Department of Pathology, Wayne State University, Karmanos Cancer Institute, Detroit Michigan, USA
Submitted July 8, 2010 - Accepted for Publication September 15, 2010
KEYWORDS: Prostate adenocarcinoma; Brain metastasis; Hormonal therapy
CORRESPONDENCE: Ashish Bhargava, MD, Department of Internal Medicine, 2E University Health Center, 4201 St. Antoine, Detroit, MI 48201, USA ().
CITATION: UroToday Int J. 2010 Oct;3(5). doi:10.3834/uij.1944-5784.2010.10.11
ABBREVIATIONS AND ACRONYMS: CT, computed tomography; MRI, magnetic resonance image; PSA, prostate-specific antigen.
The advent of the prostate-specific antigen (PSA) screening test has resulted in diagnosis of prostate cancer at an early stage. Most patients are detected with elevated PSA levels; however, progression to advanced disease or initial presentation with metastasis is not uncommon.
The present case had an unusual clinical presentation of metastatic prostate cancer. Intracranial metastases from prostate adenocarcinoma are very uncommon, and initial presentation with symptomatic brain involvement is especially rare. We describe such a case of prostate cancer with metastasis to the clivus and associated soft tissue component causing neurologic deficits. A literature review of similar clinical presentations of prostate cancer was conducted and is discussed.
A 65-year-old male of African-American ethnicity was referred to our institution. He had blurred vision and diplopia of 1-month duration. He denied any associated eye pain, headache, or other ocular or neurologic symptoms. He had no significant past medical history or history of trauma or cranial injury. His ocular history was otherwise unremarkable. Upon careful history taking, the patient revealed a slightly increased frequency of urination with nocturia about twice every night in the previous 6 months. He also had a 10 lb weight loss within the last few weeks. He denied fever, hematuria, dysuria, straining, or urinary incontinence.
The patient was referred to ophthalmology for evaluation of visual complaints. His visual acuity was 25/20 in the right eye and 20/20 in the left eye. A cover test revealed esodeviation with right abduction deficit in the right eye. No visual field defects were seen. Pupils were isochoric, without evidence of a relative afferent pupillary defect. Slit lamp examination revealed mild bilateral nuclear sclerotic changes. Intraocular pressures were within normal limits, and bilateral dilated fundoscopic examination showed no evidence of papilledema. There was no ptosis. Isolated sixth cranial nerve involvement was suspected, but all other cranial nerves were found to be intact.
Due to the minor urinary complaints, a digital rectal examination was performed by the patient's primary physician. This examination revealed an enlarged nodular prostate. Laboratory testing demonstrated a PSA level of 3833 ng/mL. The remaining assessments were completely normal, including alkaline phosphatase of 91 IU/L, creatinine of 0.9 mg/dL, and hemoglobin of 14.1 g/dL. His serum PSA level, obtained at our institution, was 6190 ng/mL. Prostate volume was 76 cc on transrectal ultrasound.
Random guided biopsies were obtained. The microscopic examination of the core biopsies (Figure 1) revealed a high-grade prostatic adenocarcinoma with Gleason score 8 (4+4). There was bilateral extensive and diffuse involvement of all cores from the apex, middle, and base of the prostate.
Staging thorax, abdomen, and pelvis computed tomography (CT) demonstrated an invasive, massively enlarged, heterogeneous, and irregularly shaped prostate gland that was consistent with underlying carcinoma. There was local spread of the prostate cancer through the prostatic capsule, with invasion into the rectum and urinary bladder base. Lung metastases, liver metastases, extensive mediastinal/retroperitoneal lymphadenopathy, and extensive osseous metastatic disease with extension into the central sacral spinal canal were present. A CT scan of the cranium (Figure 2) revealed metastatic lesions within the calvarium, which included a destructive lesion with soft tissue mass involving the clivus. The size of this clivus metastasis was 2.3 cm x 3.3 cm x 2 cm in transverse, anteroposterior, and craniocaudal dimensions, respectively. There was also involvement of the Dorello canal, which contains the abducens nerve (cranial nerve VI). Subsequently, a Technetium-99m methylene diphosphonate (99mTc MDP) bone scan confirmed multiple areas of abnormally increased tracer uptake in the axial skeletal system and calvarium. These findings were consistent with metastatic disease to the bones (Figure 3).
The patient was started on combined androgen blockade therapy with a lead-in period of bicalutamide, followed by luteinizing hormone-releasing hormone (LHRH) analog therapy. At the 2-week follow-up examination, the visual symptoms and bone pain had significantly improved, PSA had declined from 6190 ng/mL to 1025 ng/mL, and the urinary symptoms had resolved. An orbital CT scan repeated after 6 months of androgen suppression therapy demonstrated that there was nearly complete resolution of the soft tissue component of the clivus metastasis (Figure 4). After 6 months of combined androgen blockade, there was complete resolution of the mediastinal and retroperitoneal adenopathy, significant interval decrease in the size of the prostatic mass, and improvement in lung and liver metastases. The current PSA nadir is 0.6 ng/mL and there is complete resolution of the visual symptoms. The patient continues on therapy.
Visual symptoms related to calvarial metastasis from prostate cancer are uncommon. Brain metastases from prostate cancer are a rare event (0.2% - 2%) , usually associated with advanced disease, and thought to have poor prognosis and low chance of 1-year survival [2,3]. Authors of a retrospective study of 7994 cases with intracranial metastasis found 38 cases from prostate cancer (0.7%) . The most common site of prostate cancer metastases remains the axial skeleton (ie, lumbar spine, pelvis, and proximal femur), although metastases to the ribs and lymph nodes are also frequent [5,6]. Another study reported that the antemortem diagnosis of intracranial metastases has been observed in only 0.1% of cases . The reported incidences at autopsy range from 0.6% to 4.4% and predominantly involve the leptomeninges (67%), followed by the cerebrum (25%), and cerebellum (8%) [5,8].
Neurologic deficits in prostate cancer can be a result of direct extension from the skull/calvarial lesion, lymphatic spread, or vascular embolization. Adenocarcinoma is the most frequent histology found, but other histologic types such as small cell carcinoma, cribriform, or transitional cell carcinomas have been described. Cranial metastases are more frequent with these unusual histologies than with adenocarcinoma [4,9,10].
Clinical manifestations of intracranial prostate cancer metastases can also be caused by hemorrhage or mass effect. Headache and cognitive changes are the most frequent symptoms of increasing intracranial pressure. Ataxia and tremor only appear when the cerebellum and cerebral trunk are involved . Other described neurological findings are motor deficits, mental status changes, gait disturbance, vertigo, multiple cranial nerve palsies, and inappropriate secretion of antidiuretic hormone syndrome . Cranial nerve palsies caused by metastases from the prostate to the clivus are uncommon .
Table 1 contains a summary of published reports of patients with intracranial prostate metastasis. Clivus metastasis from prostate cancer presenting with nerve compression is a very rare entity, but it has been described previously . The 6th cranial nerve can be affected by skull base lesions. The clivus is a single midline structure of bone at the skull base, formed from the sphenoid rostrally and the occiput caudally. The Dorello canal near the clivus can be visualized on magnetic resonance imaging (MRI), and has been described as a cerebrospinal fluid-filled invagination containing abducent nerve fibers into petroclival dura mater . It can be the site for primary tumors like chordomas, plasmocytomas, or lymphoma. Direct extension from adjacent pituitary tumors or secondary sites from the prostate, breast, and lung have been described. Clivus involvement related to prostate cancer usually occurs in advanced stages and has been associated with poor prognosis.
A retrospective study reported that the relative ratios for the occurrence of skull base, intracranial, and ocular metastasis were 11:2:1, respectively . With advancement in diagnostic technology, it follows that intracranial metastasis would be detected earlier; however, neurologic and visual symptoms as presenting signs of prostate cancer remain unlikely. Castro GÃ³mez et al  described a case of intracranial prostate metastasis that progressed despite chemotherapy and hormonal treatment. The metastasis was detected 15 months after the initial diagnosis. The patient presented with a headache; a left temporal mass was found. Surgical removal confirmed metastatic prostate adenocarcinoma. Radiotherapy was given but the patient expired after 6 months, secondary to progressive disease. A similar case was described by Sutton et al ; however, the neurologic symptoms reversed with bilateral orchiectomy. Their case presented with left-sided hemiparesis; a right parietal mass was found and surgically removed (Table 1).
Rao  and Saito et al  described intracranial metastasis with mass effect at the cavernous sinus, leading to compression of cranial nerves II, III, IV, V, and VI. Both cases presented with visual symptoms with minimal symptoms of bladder neck obstruction. The Saito et al case responded to hormonal therapy alone, with resolution of his lesion at a repeat MRI; the Rao case also responded well to intracranial surgery and hormonal therapy.
The present case was similar to the patient described by Malloy , with prostate cancer metastasis to the clivus and presentation with abduction deficits and 6th cranial nerve involvement. Neuroimaging in the Malloy case revealed metastasis to the clivus, involvement of the cavernous sinus, and smaller metastasis to the left temporal lobe with extensive bony involvement in the vertebral column. In our case, the CT scan of the skull showed destruction of the clivus and involvement of the Dorello canal, with multiple metastatic calvarium lesions without pituitary or cavernous sinus involvement. Further scans revealed extensive bone metastases to the spine, ribs, and pelvic bones, as well as extensive retroperitoneal and thoracic nodal disease, with involvement of the pleura and liver. However, there was neither a compression of the cavernous sinus nor any intraparenchymal brain lesion. It has been postulated that metastasis to the brain either occurs by: (1) direct access through the paravertebral venous plexus, avoiding the bone and viscera; or (2) a multistep chronic process whereby the initial metastatic foci are the bone or lung, with secondary seeding of tumor cells to the brain. Our case can be explained by the latter postulation. Rapid progression of these steps with initial clivus destruction was thought to be the cause of the isolated 6th cranial nerve palsy. The patient described by Malloy  was treated with intracranial radiotherapy for visual symptoms. The patient's visual symptoms responded, but within a year he presented with widespread metastatic lesions in the entire vertebral column. Interestingly, no recurrence of the intracranial lesion was noted. Our case presented with the neurologic deficit as the chief complaint despite multiple areas of widespread metastasis. The patient responded remarkably well, with complete recovery of his visual symptoms and PSA normalization after 6 months of therapy. The patient continues in remission at a follow-up of 12 months.
Prostate cancer can occasionally present with neurologic manifestations, predominantly due to metastatic involvement of the skull bone. Awareness of this possibility could lead to accurate diagnosis, and initiation of appropriate therapy can successfully reverse the neurologic deficits. With treatment, the response rates and prognosis are similar to other types of metastatic prostate cancer.
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