Keywords prostate carcinoma - dural metastasis - subdural hematoma
Introduction
Although prostate carcinoma rarely metastasizes to the central nervous system, prostate
is the most frequent primary carcinoma to metastasize to the dura mater.[1 ]
[2 ] There is wide variability in the presentation of dural metastases in terms of clinical
manifestations as well as imaging characteristics. Furthermore, there is no consensus
regarding the possible role of surgical management of this disease. Here we describe
the case of a 45-year-old gentleman with a 3-year history of castrate-resistant prostate
adenocarcinoma who presented with rapid neurologic decline in the setting of a holohemispheric
isodense subdural mass. This was initially thought to represent a subacute subdural
hematoma (SDH) and given his neurologic decline, he was taken emergently for surgical
decompression. Intraoperatively, however, this lesion was found to be massive thickening
of the dura and pathology and postoperative imaging ultimately revealed this to be
a widespread prostate carcinoma dural metastasis. We discuss the imaging findings
and management of this unusual pathology as well as review the literature related
to dural prostate carcinoma metastases both mimicking and causing SDH.
Case Report
Our patient was a 45-year-old gentleman with a 3-year history of prostate carcinoma
with bony metastases. He had previously been treated with multiple modalities including
prostatectomy, androgen deprivation therapy, leuprolide, radiation therapy to the
prostate, and chemotherapy, including docetaxel and enzalutamide. He had also received
radium therapy and abiraterone for his bony metastases. Despite his progressive disease,
he had been living independently and was functional with activities of daily living.
He presented to our center with a 4-week history of progressive headaches and dizziness,
as well as gait difficulty resulting in multiple falls. Noncontrast computed tomography
(CT) of the head demonstrated an isodense right-sided holohemispheric extra-axial
mass causing brain compression, effacement of the ventricles, and 1.2 cm of right-to-left
midline shift ([Fig. 1A ]). Given his recent falls, this imaging finding was thought to be most consistent
with a subacute SDH, although the borders between the extra-axial mass and cortex
were noted to be non-distinct. While further imaging with magnetic resonance imaging
(MRI) was considered, the patient soon exhibited rapid neurologic decline, including
severe confusion and agitation. This rapid clinical change made treatment of the mass
effect more urgent than when he initially presented and ruled out obtaining MRI as
an unacceptable delay to treatment; in his agitated state, it was also unclear whether
the patient would tolerate the positioning required for high-resolution MRI without
intubation. Given the extent of mass effect and rapid neurologic change, as well as
the suspicion that the underlying etiology was a subacute SDH, the option of surgical
evacuation was discussed with the patient's family and he was ultimately taken to
the operating room for a craniotomy for evacuation.
Fig. 1 (A ) Preoperative noncontrast computed tomography (CT) of the head, axial view, showing
a right-sided holohemispheric isodense mass causing significant mass effect. Note
the indistinct borders between the mass and cerebral cortex. (B ) Postoperative noncontrast CT of the head, axial view, showing partial decompression
of the mass effect by hemicraniectomy. (C ) Bone windows of the preoperative CT demonstrate patchy hyperostosis along the inner
table of the calvarium (arrow). (D ) Postoperative contrast-enhanced magnetic resonance imaging of the brain, coronal
view, showing a holohemispheric right subdural mass with heterogeneous contrast enhancement.
A large trauma craniotomy was performed and the dura was noted to be tense. Several
small firm nodules were also noted to arise from the dura and the inner table of the
the skull was irregular. A linear opening was made in the center of the dura revealing
significant thickening of the dura consistent with dural tumor. Several specimen were
sent to pathology. There was no evidence of underlying SDH and the decision was made
to forego any further tumor resection. The dural defect was covered with a Duragen
onlay (Integra LifeSciences, New Jersey, United States) and the myocutaneous flap
was closed, leaving out the bone flap to allow for decompression. Postoperatively,
the patient's neurologic exam improved. A postoperative head CT demonstrated partial
decompression of the mass effect ([Fig. 1B ]) and review of the preoperative head CT bone windows revealed foci of patchy hyperostosis
along the inner table ([Fig. 1C ]). A postoperative MRI confirmed extensive dural thickening and enhancement consistent
with dural-based metastatic disease ([Fig. 1D ]). Histologic analysis of the epidural and dural specimen was consistent with metastatic
adenocarcinoma with large glandular patterns consistent with prostate primary. Immunohistochemical
stains were positive for prostate-specific antigen, prostate-specific membrane antigen,
and NKX3.1 ([Fig. 2 ]). Given the advanced status of his metastatic disease and inoperable nature of his
dural metastasis, the decision was made to pursue palliative care and home hospice.
Fig. 2 Microscopic images of intraoperative specimens sent for pathological analysis. Hemotoxylin
and eosin (H&E) staining (A ) as well as immunostaining of the intraoperative specimens (B–D ). Scale bars are indicated in the bottom right for each image. Microscopic evaluation
reveals a metastatic adenocarcinoma with large glandular patterns and necrosis (A ). The tumor cells are immunopostive for prostate-specific antigen (PSA), prostate-specific
membrane antigen (PSMA), and NKX3.1, consistent with a prostate primary (B–D ).
Discussion
Prostate adenocarcinoma is one of the most common primary cancers to metastasize to
the dura, comprising 19.5% of cases reviewed by Laigle-Donadey et al.[1 ] Breast (16.5%), lung (11%), and stomach (7.5%) followed in prevalence. This is in
contrast to intracerebral metastases, where prostate has been identified in less than
1% of cases.[3 ] Interestingly, there are several cases in the literature of a large prostate carcinoma
dural metastasis mimicking SDH. We identified eight such cases in addition to our
own ([Table 1 ]).[4 ]
[5 ]
[6 ]
[7 ]
[8 ]
[9 ]
[10 ]
[11 ] The age at presentation of these cases ranged from 45 to 76 years (mean 63.9 years).
The most frequent presenting symptom was headache (56%), followed by altered mental
status/confusion (44%), motor deficits (44%), and gait ataxia (33%). One patient presented
with seizures and one patient was neurologically intact on presentation. Regarding
imaging characteristics, the most common CT finding was a hyperdense collection (44%)
followed by a mixed density collection (33%). Isodense collections were relatively
rare (22%) and there were no reports of hypodense collections in this group. Surgical
management utilizing craniectomy, craniotomy, or burr holes was performed in all but
one case. Three cases were started with burr holes but then converted to craniotomy
upon encountering dural tumor instead of hematoma.[4 ]
[7 ]
[9 ] Medical management was elected in just one case where the diagnosis of metastatic
dural-based tumor was made by contrast-enhanced MRI, as opposed to pathologic diagnosis
in the other eight cases.[8 ] Neurologic improvement was reported in 44%, whereas neurological deterioration,
no improvement, or no follow-up were reported for the remaining cases.
Table 1
Reported cases of prostate carcinoma dural metastases mimicking a subdural hematoma
Study
Age
Presentation
CT imaging
Management/approach
Surgical findings (management)
Outcome
Tomlin and Alleyne, 2002[4 ]
61
Progressive headache, fatigue, altered mental status, left hemiparesis
Hypo/isodense
Frontal burr hole expanded to craniotomy
Thickened, nodular dura, greyish tumor (partial resection), no hematoma
Died 3 months after surgery
Barrett et al, 2008[5 ]
59
Head trauma, neurologically intact
Hyperdense
Minicraniotomy
Thickened dura (biopsied), no hematoma
Not reported
Cheng et al, 2009[6 ]
72
Altered mental status, gait ataxia
Isodense
Craniectomy
Thickened dura with firm tumor (partial resection), brain invasion
Died 4 months postop
Patil et al, 2010[7 ]
71
Headaches, dizziness
Hypo/isodense
Two burr holes expanded to craniotomy
En plaque extra-axial mass (biopsied)
Improved neurologically, underwent whole brain radiotherapy
Yu et al, 2012[8 ]
62
Left arm weakness, partial seizures
Hyperdense
Whole brain radiotherapy
—
Not reported
Nzokou et al, 2015[9 ]
65
Headache, confusion, arm weakness
Hyperdense
Parietal burr hole expanded to craniectomy
En plaque subdural tumor (partial resection), no hematoma
Recovered strength, discharged home, died 5 months postop
Bourdillon et al, 2016[10 ]
76
Headaches, hemiparesis
Hypo/hyperdense
Burr hole
Fibrous lesion (biopsied), no hematoma
Clear neurological improvement, elected for palliative care postop
Nunno et al, 2018[11 ]
64
Altered mental status, headache, gait ataxia
Hyperdense
Bilateral frontotemproal craniotomies
Thickened dura under high pressure (partial resection)
Comfort care
Present study
45
Altered mental status, gait ataxia
Isodense
Craniectomy
Thickened, nodular dura (biopsied), no hematoma
Improved neurologically, elected for comfort care
Abbreviation: CT, computed tomography.
Prostate carcinoma is not the only primary cancer reported to mimic SDH. Catana et
al recently reviewed mimics of SDH and reported cases of lung and breast cancer, lymphoma,
and sarcoma.[12 ] An early study also detailed the surgical treatment of a pancreatic adenocarcinoma
metastasis to the dura.[13 ] CT imaging characteristics are variable, with 40% of metastatic solid cancer presenting
as a hyperdense lesion, 30% as an isodense lesion, 10% as a hypodense lesion, and
20% as a mixed density lesion.[12 ] Similar findings were seen with lymphoma and sarcoma, with a hyperdense extra-axial
lesion as the most common CT finding.[12 ] Apart from the density of the lesion on CT, Nunno et al also pointed to the nodular
character of the lesion on imaging, which may help distinguish SDH from a dural metastasis.[11 ]
There are several proposed mechanisms by which prostate carcinoma may metastasize
to the dura. Direct extension from skull metastases was the most common cause of dural
metastasis in the pathological series of Laigle-Donadey et al[1 ] and Nayak et al.[2 ] Metastatic tumor cells may spread hematogenously, either via the arterial circulation
or through the venous system, such as Batson's plexus.[14 ] Transmission via the lymphatic circulation has also been suggested.[1 ] In the series of cases we identified, skull metastasis was not seen with a high
frequency, suggesting that most of the dural metastases may have resulted from hematogenous
spread or from occult bony metastases that were not apparent in surgery or on autopsy.
Interestingly, prostate dural metastases have also been associated with SDH ([Table 2 ]). Multiple hypotheses have been proposed to explain this phenomenon, including hemorrhage
from tumor vessels, effusion due to obstruction of dural vessels by tumor, and tumor-induced
vascular and fibrous proliferation within the dura.[13 ] Cheng et al also hypothesized that perhaps the membrane that forms around a chronic
SDH may serve as a conduit for metastatic cells to invade the dura.[15 ] Furthermore, the features that make the primary prostate carcinoma likely to metastasize
also promote leakiness of both tumor blood vessels and the metastatic target tissue,[16 ] making a metastasis site on the dura potentially more susceptible to subdural hemorrhage.
Hematoma formation is also more likely when these factors are compounded with the
coagulopathy secondary to malignancy that is commonly found in these patients.[16 ]
Table 2
Reported cases of prostate carcinoma dural metastases causing a subdural hematoma
Study
Age
Presentation
CT imaging
Management/approach
Surgical findings (management)
Outcome
Barolat-Romana et al, 1984[17 ]
62
Altered mental status, homonymous hemianopsia, hemiparesis
Hyperdense, ICH
Craniotomy
Large hematoma under pressure (evacuated), thickened subdural membrane (biopsied)
Resolution of neurological deficit, discharged home, doing well on 6 months follow-up
Bucci and Farhat, 1986[18 ] Case 1
62
Headache, lethargy, confusion
Isodense
Craniotomy
Hematoma (evacuated), membranes (biopsied)
No postop improvement, died POD6
Bucci and Farhat, 1986[18 ] Case 2
63
Confusion, lower extremity weakness
Hypodense
Surgical evacuation of SDH
Hematoma (evacuated), membranes (biopsied)
Mental status improved
Cheng et al, 1988[15 ]
64
Hemiparesis, gait ataxia
Hypodense
Craniotomy
Multilayered membranous hematoma with loculations (evacuated), hyperemic dura (biopsied)
Improved strength and gait, able to walk within 1 month, stable on 3 months follow-up
Cobo Dols et al, 2005[19 ]
54
Headache, facial palsy, altered mental status
Hypodense
High-dose steroids
—
No improvement, died day 7
Dorsi et al, 2010[20 ]
71
Progressive headache, aphasia, gait ataxia, hand apraxia
Hypodense
Parietotemporal craniotomy
Cyst with yellow proteinaceous fluid under extremely high pressure (evacuated), thickened
dura (biopsied)
Immediate improvement in speech and strength, intact on follow-up
George et al, 2012[21 ]
72
Progressive worsening confusion, hemiparesis
Hypodense
Frontal burr hole, required reoperation
Dark fluid (evacuated), membranes (biopsied)
Failed to improve; died 1 week postop
O'Meara et al, 2012[16 ]
62
Epistaxis, anemia, thrombocytopenia, altered mental status
Hypodense
Parietal craniotomy and contralateral parietal burr hole
Thickened dura, subdural membranes (biopsied)
Recovered well but declined POD2, died POD4
Boukas et al, 2015[22 ]
75
Dysphasia, gait ataxia, falls
Hypodense
Two burr holes, reoperated POD5
Light brown hematoma under high pressure (evacuated), subdural membranes (biopsied)
Slow, fluctuating recovery; underwent whole brain radiotherapy, then comfort care,
died 2 months postop
Caruso et al, 2017[23 ]
79
Cognitive-motor slowing
Hypodense
High-dose steroids
—
Not reported
Önen et al, 2017[24 ]
71
Altered mental status (coma), anisocoria, left hemiplegia
Not reported
Craniotomy
Hematoma (evacuated), extra- and intracalvarial and extra- and intradural metastases
(biopsied)
Did not improve, died POD4
Lippa et al, 2017[25 ]
80
Comatose with unilateral blown pupil
Hyper/hypodense
Burr hole
Hematoma evacuated; bone fragments from burr hole sent to pathology
Rebled and died within 24 hours
Abbreviations: CT, computed tomography; ICH, intracerebral hemorrhage; POD, postoperative
day; SDH, subdural hematoma.
The diagnostic ambiguity between dural metastasis and SDH (regardless of chronicity)
is a common thread among several cases from the literature, including our own.[4 ]
[5 ]
[6 ]
[7 ]
[10 ] All of the cases of dural metastases that we identified presented with either a
hyperdense, mixed density, or isodense lesion ([Table 1 ]). In contrast, the majority of true SDHs that were associated with prostate metastases
presented as a hypodense lesion ([Table 2 ]), a difference that is statistically significant between these two small cohorts
(p = 0.004, Fisher's exact test). Ascertaining lesion nodularity on CT imaging may be
difficult, especially with isodense lesions as in our case. CT bone windows in our
case also demonstrated patchy hyperostosis along the inner table of the skull, suggesting
the presence of metastatic disease. Finally, contrast-enhanced MRI can better distinguish
between hematoma and tumor. In our case, the patient's rapid neurologic decline and
poor mental status combined with our suspicion for SDH led to surgical decompression
without first obtaining an MRI.
In the series of all dural metastases mimicking SDHs by Catana et al, 71% (34 patients)
were treated surgically.[12 ] Among these surgical patients, 65% had resolution of symptoms. Our results show
that in a subset of prostate carcinoma patients treated surgically, 44% showed improvement
([Table 1 ]). Catana et al also found that management strategy was not correlated with improved
functional outcomes or with improved mortality.[12 ] This is also similar to our literature review of prostate cancer, in that the mode
of surgical treatment did not ultimately affect outcomes. It is important to note
that, as with our case, these patients were most often taken to surgery with the presumption
that they had a SDH, and not extensive metastatic disease. Such metastatic disease
is known to be a poor prognosis,[11 ] and distinguishing it from SDH may sway patients, families, and surgeons away from
aggressive surgical management.
This mounting literature points to some new suggested practices for practitioners.
In patients with prostate malignancy, even with a clear history of trauma, the differential
diagnosis between SDH and extra-axial metastasis should always be considered. Prior
groups have suggested that a CT with contrast should be performed in these circumstances.[5 ]
[15 ] In fact this was done in one case,[8 ] where the contrast-enhanced CT scan was diagnostic and was confirmed by subsequent
MRI. Cheng et al, have also suggested that any brain hemorrhage in a patient with
known metastatic prostate carcinoma should be investigated for dural and/or intracranial
metastasis.[15 ] We agree that practitioners should be vigilant and keep dural metastasis on the
differential when evaluating patients with imaging evidence of a SDH. If the patient
is stable, contrast-enhanced MRI is a suitable next step after noncontrast CT, as
it provides more detailed information regarding the nature of the lesion. Contrast-enhanced
CT may provide a “quick look” in an otherwise unstable patient in which MRI is unsafe
or not possible.
In conclusion, prostate carcinoma is the most common cancer to metastasize to the
dura and can rarely manifest as a large, holohemispheric dural lesion that mimics
acute or subacute SDH on CT imaging. Such metastatic disease should be on the differential
diagnosis in patients with advanced prostate cancer presenting with extra-axial masses,
and MRI can be obtained to distinguish between metastatic disease and hematoma. In
our literature review, 44% of patients who underwent surgical decompression demonstrated
neurological improvement. Surgical decompression may therefore be a reasonable palliative
option in carefully selected patients with symptomatic mass effect from dural metastases
of prostate carcinoma.
