Introduction/Background
Advancements in prostate magnetic resonance imaging (MRI), along with the Prostate
Imaging Reporting and Data System (PI-RADS) scoring system, have changed the management
of prostate cancer (PCa). Initial clinical guidelines in 2012 for multiparametric
prostate MRI (mpMRI) included the original PI-RADS reporting system.[1] This was followed by an updated PI-RADS version 2 in 2015 and another update, PI-RADS
version 2.1, in 2019.[2] These guidelines have profoundly impacted the detection of PCa, particularly clinically
significant PCa (csPCa), with a recent meta-analysis showing a 94% accuracy of mpMRI
for csPCa.[3]
However, the utility of the PI-RADS scoring system is limited by false positives (FPs)
and false negatives (FNs), lowering the positive predictive value (PPV) and negative
predictive value (NPV). A recent large multicenter study demonstrated PPV of 35% (interquartile
range [IQR], 27–44%) for a PI-RADS score ≥3/5 and 49% (IQR, 27–48%) for a PI-RADS
score ≥4/5.[4] Thus, the PPV was low and varied widely across centers. The NPV of mpMRI is higher
in comparison, with a meta-analysis showing an NPV of 88.1% (IQR, 85.7–92.3) for csPCa,[5] with negative defined as PI-RADS categories 1 and 2. Of note, the definition of
positive mpMRI has varied in the literature as a score ≥3/5 or ≥4/5. PPV and NPV influence
the test's utility and affect decision-making. Therefore, this review aims to highlight
some pitfalls that are the common cause of FP and FN, which, if avoided, could improve
the test's utility.
Discussion
PI-RADS version 2.1 has defined the primary sequences used in determining the overall
suspicion for csPCa (dominant sequence) for the peripheral and transition zones (TZs).
The abnormalities on the dominant sequence for a respective zone carry higher weightage.
For the peripheral prostate zone (PZ), apparent diffusion coefficient (ADC) map with
diffusion-weighted imaging (DWI) utilizing high b values (≥1,400 s/mm2) is the dominant sequence. The dominant sequence for the TZ is the T2-weighted imaging
(T2WI). A mimic or pitfall affecting a particular zone on its dominant sequence has
a higher potential of causing diagnostic confusion within that zone.
Pitfalls Causing False Negatives (FNs)
FNs Related to MRI Technique
Pitfalls related to the MR technique are primarily seen in association with diffusion
imaging. While allowing rapid acquisition, DWI also warrants technique optimization
due to extreme sensitivity to susceptibility and motion. It is often performed as
an axial-free breathing echo-planar technique combined with spectral fat saturation.
-
Susceptibility and motion artifacts: DWI acquisition with echo-planar imaging (EPI) involves rapidly changing strong
magnetic field gradients. This can induce superimposed magnetic fields via the induction
of eddy current, which can ultimately cause anatomical distortion of the prostate
structures compared to the T2WI. Sources of magnetic field heterogeneity, such as
gas, calcium, or metal in the prostate region, worsen this problem ([Fig. 1A–F]). This can present as stretching and distortion of the prostate boundary, surgical
capsule, or focal lesions, along with shape deformation and spatial misregistration.
Similar anatomical distortion can occur with motion, often related to rectal peristalsis,
affecting the T2WI and DWI sequences.
Fig. 1 (A) Axial T2-weighted image (T2WI; arrow) shows a focal lesion exhibiting moderate hypointensity in the right mid-gland prostate
zone (PZ). (B) Diffusion-weighted imaging (DWI; arrow) and (C) apparent diffusion coefficient (ADC) map (arrow) show no discrete corresponding DWI hyperintense or ADC hypointense abnormality;
however, it can be seen that the susceptibility artifact from rectal gas degrades
the assessment of the most posterior aspect of the PZ. (D) On subsequent magnetic resonance imaging (MRI), axial T2WI (arrow) shows a similar focal lesion, which is now clearly noted to exhibit marked diffusion
restriction on DWI (arrow) and (F) ADC map (arrow). Biopsy showed Gleason 3 + 4 prostate cancer (PCa) in the right mid-gland. In another
patient, there is a band of artifacts related to rectal stool and gas (white arrows) seen extending horizontally on both (G) DWI and (H) ADC. Since DWI was performed with the phase encoding direction switched side to
side as part of routine prostate imaging protocol, this prevented the band of artifact
from propagating onto the prostate, which could have otherwise obscured the diffusion-restricting
PI-RADS 4 lesion (yellow arrows in G and H) exhibiting (I) focal hypointensity on T2WI with (J) early enhancement. The T2 hypointense area in the left PZ was considered a postinflammatory
change considering the well-demarcated margins.
Pearls
Image acquisition, particularly DWI, can be optimized to mitigate the above-described
artifacts. The phase encoding direction can be switched routinely to side to side
for DWI to avoid propagation of the artifacts related to rectal stool/gas onto the
prostate ([Fig. 1G–J]). This contrasts the routinely performed anterior to posterior phase encoding in
the pelvic MRI based on relatively shorter pelvic dimension than side to side. Patients
may also be encouraged to evacuate the rectum or enema may be considered just before
the MRI to reduce the artifacts from gas, stool, and peristalsis. Occasionally, placing
rectal catheters to remove gas or administering water-based gel can help if susceptibility
from stool or gas still degrades the examination. Although bowel peristalsis can be
reduced by using antispasmodic agents such as glucagon or hyoscyamine, their use is
not essential; it needs to be weighed against the increased costs and potential side
effects.[6] Utilizing 1.5-T MRI instead of the 3-T MRI can specifically be considered in patients
with pelvic metal prostheses (e.g., hip arthroplasty) to reduce the associated susceptibility
artifacts.
-
Improper b-value selection for DWI: While b-values of up to 1,000 s/mm2 are often sufficient in most DWI assessments of abdominopelvic organs, the background
benign prostate parenchyma is not sufficiently suppressed on such b-values to allow optimal neoplasm detection. The utility of high b-values in the 1,400 to 2,000 s/mm2 range has been demonstrated in optimizing the conspicuity of csPCa,[7] most of which restrict diffusion, allowing them to appear sufficiently hyperintense
relative to the background parenchyma.
Pearls
A high b-value (≥1,400 s/mm2) image set is mandatory per the PI-RADS committee recommendations, with a b-value of 1,600 to 2,000 s/mm2 often preferred.[7] Low (0–100 s/mm2) and intermediate (800–1,000 s/mm2) b-values are utilized for ADC calculation. The required high b-value (≥1,400 s/mm2) can either be calculated from the low/intermediate b-values or acquired separately. However, the high b-value DWI should not be included in the ADC map generation to avoid diffusion kurtosis
effect on ADC, resulting in lower-than-expected ADC.
-
Suboptimal viewing of DWI/ADC: The PI-RADS criteria for DWI/ADC maps are based on qualitative visual assessment.
Optimal assessment requires that these sequences be viewed with consistently similar
contrast. Notably, the default window settings on the picture archiving and communication
system (PACS) may not allow the tumor to be sufficiently conspicuous from the background
parenchyma.
Pearls
Due to the variable DWI acquisition technique, the optimal window settings may need
to be determined for each system. The window level and width settings of 1,400/1,400
for the ADC map may be used as a starting point, but this may not be ideal for all
systems. The levels should be adjusted to visualize csPCa as markedly hyperintense
on high b-value DWI and markedly hypointense on ADC maps. A quantitative ADC threshold of less
than 750 to 900 μm2/s may help differentiate malignant from benign tissue in PZ (lower value favoring
csPCa).[8] However, the routine clinical utility of such thresholds is limited by the potential
technical variability of ADC and overlap of ADC between benign and malignant lesions.
-
Artifacts related to the use of endorectal coil (ERC): Using an ERC is optional based on the PI-RADS recommendations. Surface coils with
a sufficiently high number of external phased array coil elements and radiofrequency
(RF) channels (16 or more) can provide adequate signal-to-noise ratio (SNR)/image
quality without ERC, even with 1.5-T MRI. However, ERC can increase the SNR at any
MR field strength. It can be advantageous, such as in some older 1.5-T MR systems,
with larger patients where SNR is limited with external coils alone or where particularly
high spatial resolution is desired for staging purposes. Besides the time, patient
preference, and cost considerations, ERC use is associated with gland deformation
and additional artifacts. ERC balloons utilizing air can introduce another source
of susceptibility artifacts. Improper placement of the ERC antenna can cause artifacts
mimicking malignancy.
Pearls
ERC should be positioned in a plane perpendicular to the side-to-side phase encoding
direction to avoid artifactual focal diffusion restriction on DWI and enhancement
adjacent to the coil. Since these artifacts do not affect T2WI and ADC map, correlating
with these sequences will also avoid mislabeling these findings as pathologic. It
is recommended that the ERC antenna be placed from the 10 o'clock position to the
2 o'clock position. ERC balloon alternatives without air are available to prevent
associated susceptibility.
FNs Related to Variants and Unusual Patterns of Prostate Malignancies
-
Mucinous adenocarcinoma: The mucinous subtype of prostate adenocarcinoma is rare, accounting for approximately
0.4% of all prostate adenocarcinomas.[9] It is diagnosed when greater than 25% of the tumor contains clustered cells floating
in mucin lakes. Imaging diagnosis is challenging since appearance deviates from the
typical nonmucinous adenocarcinoma. Thus, conventional PI-RADS-based interpretation
designed for nonmucinous PCa fails to be applied to mucinous adenocarcinoma. The tumor's
mucinous content leads to hyperintensity on T2WI, resembling cystic BPH, abscess,
or other benign lesions. Unlike typical adenocarcinoma, it usually does not exhibit
diffusion restriction. Although it may appear hyperintense on high b-value DWI, minimal to no hypointensity is observed on ADC maps.[10] In some cases, mucinous adenocarcinoma can present as isointense with the normal
PZ tissue.[11] Diagnosis remains challenging even with biopsy due to the paucity of cells obtained.
Therefore, it is crucial to be aware of this rare variant and recognize the appearance
of this entity on MRI.
Pearls
The typical appearance of multilocular cystic mass with T2 hyperintensity and dynamic
contrast-enhanced (DCE) MRI showing enhancing septations should raise suspicion for
this rare subtype, even without diffusion restriction ([Fig. 2]).
Fig. 2 (A) Axial and (B) coronal T2-weighted images (T2WIs) show a heterogeneous T2 hyperintense mass involving
the bilateral posterior peripheral zone (PZ; arrow). The lesion does not restrict diffusion, as evidenced by the absence of (C) hyperintensity on diffusion-weighted imaging (DWI; arrow) or hypointensity on (D) apparent diffusion coefficient (ADC) map (arrow), different from the background adjacent PZ. Lesion exhibits (E) hypointensity on T1WI (arrow) with (F) early arterial enhancement on DCE (arrow). Prostate biopsy showed adenocarcinoma up to Gleason score 4 + 5 = 9 with mucinous
features.
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Cribriform adenocarcinoma: Typical acinar morphology is observed in over 90% of PCa.[9] However, a predominant cribriform morphology exists among the spectrum of variants
of prostatic adenocarcinoma and impairs csPCa detection.[12] In a study, predominant cribriform morphology accounted for 22% of patients with
csPCa that had negative mpMRI,[5] with another study demonstrating that only 17% of cribriform histologic tumor types
were detected on imaging.[9] Yet others have suggested a high detection rate of PCa with cribriform patterns.[13] Our own experience suggests that these lesions may be difficult to detect, particularly
if the technique is not optimal or if the reader has limited experience. This difficult
detection is possibly related to sparse cellular structure with higher water content,
leading to higher T2 signal and less diffusion restriction ([Fig. 3]). Detection is important given recent evidence of cribriform morphology to be an
aggressive PCa pattern with higher cancer-specific mortality.[9]
Fig. 3 (A) Axial T2-weighted image (T2WI; arrow) shows a focal area of mild to moderate hypointensity in the right peripheral zone
(PZ). There is corresponding moderate diffusion restriction with (B) heterogeneous stippled hyperintensity on high b-value diffusion-weighted imaging (DWI; arrow) and (C) hypointensity on apparent diffusion coefficient (ADC) map (arrow) with (D) positive early enhancement (arrow). Biopsy revealed Gleason 4 + 3 adenocarcinoma with a cribriform pattern.
Pearls
While no distinctive imaging features have been conclusively associated with this
histologic subtype, some have suggested lower ADC values than tumors without these
patterns.[10] However, this is yet to be confirmed and contrasts the findings mentioned above
from others, suggesting less diffusion restriction of these lesions.
Pearls
Diffuse high-grade cancer tends to have lower signal intensity (SI) on T2WI and more
marked diffusion restriction, resulting in lower SI on ADC and higher SI on DWI, compared
to prostatitis. Another finding suggestive of infiltrative high-grade cancer is the
loss of normal zonal anatomy with the obliteration of the surgical capsule ([Fig. 4]).
Fig. 4 There is diffuse infiltrative moderate hypointensity on (A) T2-weighted image (T2WI; arrows) throughout bilateral peripheral zones. There is corresponding marked diffusion restriction
with marked (B) diffusion-weighted imaging (DWI) hyperintensity (arrows) and (C) apparent diffusion coefficient (ADC) hypointensity (arrows), with (D) early arterial enhancement (arrows). On T2WI (A), note the loss of zonal anatomy with obliteration of the surgical capsule
between the peripheral zone (PZ) and transitional zone (TZ). Also note the (E) T2 hypointense (arrow), (F) DWI hyperintense diffusion restricting (arrow) extraprostatic extension obliterating the left rectoprostatic angle, with (G) pelvic lymphadenopathy (caliper). Prostate biopsy showed a total of 17/20 cores
positive for up to Gleason 5 + 4 disease with 100% maximum involvement.
Pitfalls Causing False Positives (FPs)
FPs Related to Benign Pathologies
-
Acute or chronic prostatitis: This is the most common cause of FP finding for PCa.[14] Prostatitis can be acute or chronic and the signal abnormalities may suggest csPCa
on any of the mpMRI sequences. They may include an area of hypointensity on T2WI,
often in the PZ close to the anatomical capsule, with a corresponding area of hypointensity
on the ADC map and early arterial enhancement on DCE MRI ([Fig. 5]).
Fig. 5 Axial (A) T2-weighted image (T2WI; arrows) shows focal moderate hypointensity in the right peripheral zone (PZ) and transitional
zone (TZ) with (B) early enhancement (arrows). There is corresponding marked diffusion restriction with (C) hyperintensity on high b-value diffusion-weighted imaging (DWI; arrows) and (D) hypointensity on apparent diffusion coefficient (ADC) map (arrows). Biopsy of this PI-RADS 5 lesion revealed prostatitis. In another patient, (E) a wedge-shaped hypointensity on T2WI (arrow) also exhibits marked diffusion restriction on (F) high b-value DWI (arrow) and (G) ADC map (arrow). A biopsy of this lesion showed Gleason 3 + 3 adenocarcinoma. Note that although
the focal T2 hypointensity (arrow in E) is bandlike, it parallels the capsule rather than bridging anatomical and surgical
capsules.
Pearls
Morphology of the signal abnormality is often helpful in classifying an otherwise
suspicious signal abnormality as secondary to a benign inflammatory process. Inflammation
or postinflammatory changes are usually linear, wedge-shaped, or non-mass-like instead
of rounded, defined, masslike areas of signal abnormality exhibited by the PCa. Distribution
of the signal abnormality is often also helpful, with diffuse involvement suggesting
inflammatory etiology as opposed to a focal signal abnormality typically seen with
PCa. Another feature to keep in mind is the orientation of the abnormal signal. While
the linear/bandlike shape of signal abnormality favors benignity, it should bridge
the anatomical and surgical capsule rather than paralleling the capsule. Despite these
differences, appearances can overlap, and sometimes, a confident differentiation between
inflammation-related changes and csPCa may be difficult ([Fig. 5]). In such instances, a reasonable approach may involve a targeted biopsy and a repeat
MRI after 6 months or greater if the targeted biopsy demonstrates benign pathology.
A decision may then be made regarding continued imaging surveillance or repeating
the biopsy based on the appearance on follow-up imaging.
-
Granulomatous prostatitis: While most cases of granulomatous prostatitis are idiopathic, we most likely see
it secondary to intravesical bacillus Calmette–Guerin (BCG) therapy for urinary bladder
cancer.[15] On mpMRI, this can demonstrate a discrete masslike appearance with marked signal
abnormalities, including hypointensity on T2WI and ADC, hyperintensity on DWI, and
possibly periprostatic fat stranding mimicking extracapsular extension, falsely suggesting
csPCa. The signal abnormalities are often more pronounced than those with other forms
of infectious prostatitis,[16] such that often a biopsy is necessary to rule out malignancy ([Fig. 6A–E]).
Fig. 6 Multifocal lesions in bilateral peripheral zone (PZ) and left transitional zone (TZ)
exhibiting (A) marked hyperintensity on diffusion-weighted imaging (DWI; arrows), (B) marked hypointensity on apparent diffusion coefficient (ADC; arrows), and (C) positive DCE (arrows). (D) The lesions are homogenously hypointense on T2-weighted image (T2WI; arrows), with the left TZ lesion exhibiting moderate lenticular hypointensity. (E) There is broad-based capsular abutment, multifocal capsular bulging, and extracapsular
extension cranially as seen on coronal T2WI (arrows), consistent with PI-RADS 5, and suspicious for multifocal clinically significant
prostate cancers. Subsequent biopsy findings were consistent with nonspecific granulomatous
prostatitis. In a different patient with a history of intravesical Bacillus Calmette–Guérin
(BCG) therapy for urinary bladder cancer, (F) axial T2WI (arrow) shows a moderately hypointense lesion in the left PZ, with (G) corresponding marked diffusion restriction on high b-value DWI (arrow) and (H) ADC map (arrow). (I) However, note the absence of enhancement of the lesion (arrow), suggesting necrosis, which suggests BCG-related granulomatous prostatitis in this
patient.
Pearls
A helpful clue that, if present, may suggest this diagnosis and avoid biopsy includes
the presence of peripheral enhancement with the central nonenhancing necrotic region
([Fig. 6F–I]).
While a masslike appearance of granulomatous prostatitis without central necrosis
can be exceedingly difficult to differentiate from csPCa and may require histopathologic
confirmation, a history of intravesical BCG therapy may be a clue toward diagnosing
granulomatous prostatitis by increasing the pretest probability of this benign diagnosis.
-
Prostatic abscess: A prostatic abscess may complicate acute bacterial prostatitis with a distinct clinical
presentation of fever, dysuria, and digital rectal examination (DRE) eliciting tenderness
even with gentle palpation, often with fluctuance.
If imaging is desired based on clinical suspicion of complicated bacterial prostatitis,
transabdominal ultrasound is preferred. The appearance is typical of abscesses at
other sites, demonstrating a complex collection within the prostate exhibiting peripheral
vascularity. If mpMRI is performed, imaging appearance of a typical abscess, including
a circumscribed region of marked hyperintensity on high b-value DWI, with corresponding marked hypointensity on ADC,[17] may mimic csPCa based on PI-RADS assessment.
Pearls
The first clue suggesting a diagnosis of a prostatic abscess would be a typical clinical
picture as described earlier. The imaging clues to diagnosing an abscess rather than
PCa include hyperintense or heterogeneous hypointense signal on T2WI and peripheral
enhancement on DCE ([Fig. 7]).
Fig. 7 Focal lesion in right anterior transitional zone (TZ) shows marked diffusion restriction
with (A) marked hyperintensity on diffusion-weighted imaging (DWI; arrow) and (B) marked hypointensity on the apparent diffusion coefficient (ADC) map (arrow). Features suggestive of abscess were the patient's clinical setting, homogeneous
central hyperintensity on (C) axial (arrow) and (D) coronal T2-weighted image (T2WI; arrow), with peripheral enhancement on (E) postcontrast T1WI (arrow).
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Stromal BPH nodules in TZ: Benign prostatic hyperplasia (BPH) results from benign proliferation of prostatic
epithelial and stromal cells in the TZ.[18] The SI of BPH nodules on T2WI depends on the proportion of stromal versus glandular
elements. A greater percentage of glandular elements leads to higher SI on T2WI related
to higher fluid within glandular secretions.[19]
[20] BPH nodules may also often demonstrate a mixed stromal and glandular appearance
reflected by a heterogeneous signal on T2WI. A characteristic feature of stromal BPH
nodules is their T2 hypointensity, unlike the T2 hyperintense glandular BPH nodules.
This hypointense appearance on T2WI can cause the stromal BPH nodules in the TZ to
be spuriously deemed highly suspicious for csPCa. This problem is compounded by the
often-heterogeneous multinodular appearance of the TZ in patients with BPH, which
generally makes detecting TZ tumors more difficult than PZ tumors.[21] Up to 30% of PCas arise from the TZ[22] and are also more frequently missed during standard prostate biopsies,[23] necessitating their accurate identification on mpMRI.
Pearls
An important feature favoring BPH nodules over the TZ PCa is the presence of discrete
margins and an oval or spherical shape. Furthermore, a T2 hypointense capsule and
T2 hypointensity lower than expected from PCa can provide additional clues ([Fig. 8]). Internal foci of T2 hyperintensity may be observed in some stromal BPH nodules,
along with only mild diffusion restriction, sometimes only on ADC maps or DWI. Additionally,
the enhancement of these nodules is typically similar to other benign nodules within
the prostate, rather than appearing earlier and more robust than the rest of the prostate,
which is characteristic of PCa.
Fig. 8 Axial (A) T2-weighted image (T2WI; arrow) shows a lentiform homogenously hypointense focal lesion in the left anterior base
transitional zone (TZ) exhibiting marked (B) diffusion restriction on diffusion-weighted imaging (DWI; arrow) and (C) apparent diffusion coefficient (ADC) map (arrow). The lesion's marked hypointensity and partial encapsulation, confirmed on (D) multiplanar T2W sagittal (arrow) and (E) coronal (arrow) images, suggest a stromal benign prostatic hyperplasia (BPH) nodule rather than
a suspicious TZ lesion. This was correctly labeled as Prostate Imaging Reporting and
Data System 2 (PI-RADS 2). A targeted prostate biopsy was subsequently performed and
showed benign tissue.
This is usually in contrast to the noncircumscribed or lenticular shape, or irregular
margins seen with TZ malignancy.[24]
[25] TZ malignancy can also be diagnosed when a clearly invasive behavior, such as extension
into anterior fibromuscular stroma (AFS) or extraprostatic extension (EPE) is noted.
-
Extruded BPH nodules in the PZ: Extruded BPH nodules in the PZ present a unique diagnostic challenge. These nodules
result from the extension of BPH tissue from the TZ into the PZ and often abut the
surgical capsule. They appear as focal nodules, often demonstrating hypointensity
on T2WI that can show hyperintensity on high b-value DWI, hypointensity on ADC, and early enhancement. This appearance, especially
that of a diffusion-restricting lesion in the PZ, mimics csPCa based on PI-RADS assessment.
Pearls
The presence of a capsule is extremely helpful in characterizing a typical BPH nodule.
Another pearl is to utilize multiplanar T2WI, particularly sagittal and coronal planes.
This can aid in identifying the capsule surrounding the nodule and demonstrate the
continuity of the suspected signal abnormality with the BPH nodule arising from the
TZ. Additionally, hyperintense foci on T2WI corresponding to the dilated acini may
suggest extruded BPH nodules over PCa. These findings can increase diagnostic confidence
and prevent overdiagnosing ectopic BPH nodules as malignancy ([Fig. 9A–F]).
Fig. 9 (A-F) A focal lesion in the left apical peripheral zone (PZ) exhibits (A) marked hyperintensity on high b-value diffusion-weighted imaging (DWI; arrow) and (B) marked hypointensity on apparent diffusion coefficient (ADC; arrow), (C) with early dynamic contrast enhancement, meeting Prostate Imaging Reporting and
Data System 4 (PI-RADS 4) criteria. (D) Corresponding hypointense signal abnormality on axial T2-weighted image (T2WI (arrow) shows hyperintense foci. Moreover, there is a capsule surrounding the nodule with
continuity of the focal signal abnormality with the transitional zone (TZ), better
seen on the (E) coronal (arrow) and (F) sagittal T2WI (arrow). These findings suggest extruded benign prostatic hyperplasia (BPH) nodule in this
otherwise PI-RADS 4 lesion that showed benign prostatic tissue on a subsequent biopsy.
(G) In another patient, axial T2WI shows a large moderately hypointense focal lesion
involving most of the right PZ surrounded by a thin rim of low T2 signal intensity,
giving the appearance of an extruded BPH nodule. However, some atypical features exist,
as the nodule is not completely encapsulated. The lesion also has marked associated
diffusion restriction on (H) high b-value DWI (arrow) and (I) ADC map (arrow). (J) Coronal T2WI and (K) axial T2WI show additional extension of the lesion crossing midline to the left
posteromedial peripheral zone at the apex (arrow). Biopsy showed extensive prostatic adenocarcinoma up to Gleason score 8 (4 + 4)
with areas of perineural invasion as well as immunohistology findings supporting the
diagnosis of invasive carcinoma.
A pseudo-capsule can rarely form around PCa related to compressive or reactive peritumoral
fibrosis, and can be associated with high-grade and stage disease.[26] Therefore, an atypical appearance of a large encapsulated PZ lesion, especially
one that does not appear to be contiguous with the TZ, should raise suspicion ([Fig. 9G–K]).
-
Prostatic calcifications: Incidence and degree of calcifications within the prostate gland increase with age,
and they are prevalent after 50 years of age. They can be idiopathic or secondary
to prostatitis, BPH, trauma (including iatrogenic such urethral stents or radiation
therapy), diabetes mellitus, or even PCa.[27] They are most often believed to arise from the calcification of the corpora amylacea
that, in turn, may be related at least in part to the prostatic secretions. Prostatic
calcifications are often more easily visualized on computed tomography (CT) than on
MRI. When seen on MRI, they exhibit signal void on all sequences due to the diamagnetic
effect of these calcifications. The resulting marked hypointensity on T2WI and ADC
can mimic csPCa within the TZ or PZ.
Pearls
In addition to the dark signal on T2WI and ADC, these calcifications appear dark on
DWI at all b-values, suggesting their true nature. Moreover, they exhibit a complete absence of
enhancement. While these calcifications can be solitary, they occur more often in
clusters, which can be an additional clue to their presence. Correlation with CT,
if available, can be conclusive in their characterization ([Fig. 10]).
Fig. 10 Heterogeneous areas of signal loss on (A) axial (arrows) and (B) coronal (arrows) T2-weighted image (T2WI) within the posterior right greater than the left transition
zone, with (C) a complete absence of enhancement on DCE (arrows). A corresponding dark signal on (D) apparent diffusion coefficient (ADC; arrows) and (E) high b-value diffusion-weighted imaging (DWI; arrows) suggest signal void rather than true diffusion restriction. (F) Correlation with computed tomography (CT) confirmed corresponding calcifications
(arrows).
FPs Related to Normal Anatomical Structures
-
Central zone (CZ): This normal symmetric cone-shaped region of prostatic tissue surrounding the ejaculatory
ducts extends from the posteromedial base to mid-gland PZ, where ejaculatory ducts
open into the urethra at the verumontanum. It can be seen in up to 80% of the patients
and appears hypointense on T2WI and ADC, with mild DWI hyperintensity. Given this
appearance, it can mimic csPCa[28] arising from PZ (given the hypointensity on ADC) or TZ (given the hypointensity
on T2WI). Assessing this structure can sometimes present a challenge to even experienced
radiologists.
Pearls
A typical symmetric appearance of the CZ at the posterior prostate base and mid-gland,
with no early arterial enhancement on DCE, helps differentiate this normal structure
from PCa ([Fig. 11A–D]). Also, look for a mustache or dumbbell shape on the axial images, a teardrop or
triangular shape on coronal images, and the typical location surrounding the ejaculatory
ducts in the posteromedial base to the mid-gland PZ.
Fig. 11 (A) Axial T2-weighted image (T2WI; arrow) shows triangular hypointense area in the posterior midline peripheral zone (PZ)
at the gland base with diffusion restriction on (B) high b-value diffusion-weighted imaging (DWI; arrow) and (C) apparent diffusion coefficient (ADC) map (arrow), (D) without early enhancement (arrow). This location and appearance are consistent with the normal central zone and should
not be mistaken for a suspicious lesion, although it meets the criteria for a Prostate
Imaging Reporting and Data System 4 (PI-RADS 4) lesion. Contrast this in another patient
with (E) axial T2WI showing focal asymmetry in the left central zone (CZ) with a hypointense
signal similar to the remaining CZ (arrow). The lesion also exhibits marked diffusion restriction on (F) high b-value DWI (arrow) and (G) ADC map (arrow). (H) Note the early arterial enhancement (arrow). Biopsy showed left prostate base Gleason score 3 + 4 adenocarcinoma.
CZ accounts for less than 5% of PCa cases. Focal early enhancement within the CZ or
an asymmetry between the CZ on T2WI, ADC maps, or high b-value DWI that cannot be attributed to BPH should raise suspicion for PCa[29] ([Fig. 11E–H]).
-
Anterior fibromuscular stroma (AFS): This tissue layer in the anterior prostate lacks glandular tissue and thus cannot
give rise to PCa. Typically, it exhibits bilateral symmetry with a crescentic shape
and appears as a hypointense region on T2WI, similar to pelvic floor musculature.
There is no diffusion restriction, exhibiting hypointensity on both DWI and ADC map,
with absent early arterial enhancement. In certain cases, AFS may show thickening,
particularly in patients lacking significant TZ hypertrophy.
Pearls
Although PCa does not arise from AFS, cancer from PZ or TZ can involve AFS. Suspicious
findings may appear hyperintense on T2WI and hypointense on ADC relative to pelvic
floor musculature (typically more hypointense than the normal AFS), with hyperintensity
on DWI. Other suspicious findings include focal masslike or asymmetric enlargement
and early arterial enhancement. If this is suspected, the PI-RADS criteria should
be applied utilizing the criteria for the respective zones from which the lesion is
suspected to arise ([Fig. 12]).
Fig. 12 (A) Axial (arrow) and (B) sagittal T2-weighted images (T2WIs; arrow) show focal masslike asymmetric enlargement of the left anterior fibromuscular stroma
(AFS) appearing to arise from the left anterior peripheral zone (PZ). The lesion exhibits
a T2 intermediate signal that is higher than the normal T2 dark AFS. There are corresponding
areas of diffusion restriction with (C) marked hyperintensity on diffusion-weighted imaging (DWI; arrow) and (D) marked hypointensity apparent diffusion coefficient (ADC) map (arrow), with (E) asymmetric early arterial enhancement (arrow). This was suspicious for a Prostate Imaging Reporting and Data System 5 (PI-RADS
5) lesion from the left anterior prostate zone (PZ) invading the AFS. Subsequent radical
prostatectomy revealed a Gleason score 4 + 3 prostatic adenocarcinoma mostly present
in the left quadrants.
-
Thickened surgical/pseudo-capsule: The prostatic surgical capsule, or pseudo-capsule, refers to the fibromuscular layer
between the prostate's PZ and TZ. While this layer is loose and indistinct in normal
prostate gland without BPH, it can be thickened in response to pressure from BPH nodules
arising from the TZ.[30] On T2WI, it appears dark, and exhibits decreased ADC values, similar to csPCa.[31]
Pearls
A noteworthy characteristic is its bandlike or crescent-shaped appearance surrounding
the TZ. Given the anatomical distortion of the ADC maps, the correlation of the hypointensity
on the ADC map to the T2WI showing the typical appearance and location of the surgical
capsule can be extremely helpful in preventing mislabeling this anatomical structure
as csPCa ([Fig. 13]).
Fig. 13 A focal region in the left peripheral zone (PZ) appears mildly hyperintense on (A) high b-value diffusion-weighted imaging (DWI; arrow) and (B) markedly hypointense on apparent diffusion coefficient (ADC; arrow), raising suspicion for at least a Prostate Imaging Reporting and Data System 3 (PI-RADS
3) lesion. However, correlating with (C) axial and (D) sagittal T2-weighted image (T2WI), the lesion corresponds to the anatomical region
of the surgical capsule between the transitional zone (TZ) and the prostate zone (PZ)
with a crescent-shaped appearance (arrow), allowing more confident recognition as the thickened surgical capsule.
-
Neurovascular bundle: The neurovascular bundles course along the posterolateral aspect of the prostate
capsule on both sides, positioned at the 5 o'clock and 7 o'clock positions.[32] Due to its proximity to the PZ and imaging characteristics, including hypointensity/signal
void on the T2WI and ADC map, the neurovascular bundle might be mistaken for a suspicious
lesion within the PZ. It can also induce anatomical distortion of the prostate boundaries,
potentially leading to misinterpretation as a mass lesion within the periprostatic
space.
Pearls
The typical location along the posterolateral margins, a rounded contour on a single
axial slice, tubular morphology across consecutive slices, and bilaterally symmetric
bundles assist in resolving the suspicion.[33] The neurovascular bundles are often better assessed on T1WI, where they are recognized
as oval (when viewed axially) or linear (when viewed in the long axis), hypointense
structures surrounded by hyperintense fat. Neurovascular bundle invasion on T1WI may
appear as asymmetric enlargement with loss of the intervening periprostatic fat plane
or as gross tumor extension.[34]
-
Periprostatic venous plexus: The periprostatic venous plexus is located close to the prostate capsule, and distinguishing
it from the PZ on mpMRI can occasionally present a challenge due to low SI related
to flow void on T2WI. Occasionally, it may also exhibit mildly restricted diffusion
on EPI ([Fig. 14]), and along with focal enhancement indicating abnormal enhancement kinetic, these
findings may mimic csPCa.
Fig. 14 Diffusion restriction is noted along the lateral margins of the bilateral peripheral
zone (PZ) on (A) the high b-value diffusion-weighted imaging (DWI; arrows). (B) On correlating with T2-weighted image (T2WI; arrows), this corresponds to the bilateral periprostatic venous plexus.
Pearls
Awareness of the presence and expected location of this normal anatomical structure
around the prostate should lead to evaluating the postcontrast sequence. Delayed enhancement
would then point toward a periprostatic venous structure instead of a tumor.[35]
FPs Related to Postintervention Changes
-
Postbiopsy hemorrhage: Often, patients with suspected PCa have undergone prostate biopsy before MRI evaluation.
This may cause hemorrhage, producing MRI signal abnormalities within the prostate.
Hemorrhage-related signal changes include, more commonly, T2 hypointensity, but depending
on the age of the hemorrhage, they can also appear to restrict diffusion.[36] These changes overlap with the appearance of PCa on T2WI and DWI/ADC. Moreover,
the T1 hyperintense appearance of the hemorrhage can interfere with assessing the
region on DCE, wherein a tumor would be expected to demonstrate early enhancement.
The normal prostate gland produces citrate, which possesses anticoagulant properties.
Consequently, the hemorrhage occurring after a biopsy is more extensive and lingers
longer in the region of the normal PZ.[37] On the other hand, citrate levels are diminished in the areas affected by PCa,[38] resulting in a more rapid resolution of hemorrhage in the tumor due to the absence
of the anticoagulant effect.[39]
Pearls
It is recommended to perform mpMRI at least 6 to 8 weeks after the biopsy to allow
resolution of the hemorrhage, although hemorrhage-related changes can persist for
up to 4.5 months.[40] csPCa exhibits more discrete masslike abnormality, demonstrating more marked SI
alterations on DWI and DCE than postbiopsy hemorrhage. The hemorrhage exclusion sign
can be helpful and describes the presence on T1W images of either a well-defined area
of hypointensity in the PZ surrounded by an area of hyperintensity on at least one
side or diffuse hyperintensity within a PZ region with an abrupt cutoff outlining
a lesion. When this sign is present with a corresponding area of hypointensity on
T2WI, it can strongly suggest csPCa[36] ([Fig. 15]). T1WI subtraction postcontrast images or perfusion maps can help differentiate
actual enhancing lesion from intrinsically T1 hyperintense hemorrhagic focus.
Fig. 15 A focal lesion in the left peripheral zone (PZ) exhibiting (A) marked hyperintensity on high b-value diffusion-weighted imaging (DWI; arrows) and (B) marked hypointensity on apparent diffusion coefficient (ADC) map (arrows), (C) with patchy areas of homogenous moderate hypointensity on T2-weighted image (T2WI)
that are nonspecific in the setting of recent biopsy. (D) On pre-T1WI, a diffuse hyperintense region of hemorrhage is present throughout the
right prostate zone (PZ), with an abrupt cutoff to a region of no hemorrhage (arrows, hemorrhage exclusion sign) and corresponding focal moderate hypointensity on T2WI
(arrows in C), increasing confidence for cancer detection. Note that DCE assessment of the focal
lesion was limited by the abutting regions of (E) intrinsic T1 hyperintensity (arrows), (F) but the perfusion map clearly shows positive DCE corresponding to the focal suspicious
region (red areas marked by arrows). The lesion is thus Prostate Imaging Reporting and Data System 5 (PI-RADS 5). Prostate
biopsy showed Gleason score 4 + 4 adenocarcinoma in the left apex and mid-gland with
benign tissue in the right gland.
-
Postprostatic urethral lift (UroLift) procedure: One of the newer minimally invasive approaches to treat symptomatic BPH includes
a prostatic urethral lift with a UroLift procedure. It involves permanent metallic
implants that retract the prostatic tissue, creating a channel for urine passage.[41] This MRI conditional device is safe for use with field strengths of up to 3 T.[42] However, it causes artifacts that negatively affect the MRI quality, with a recent
study demonstrating obscuration of a third of the gland on DWI.[43]
Pearls
The potential to significantly affect the evaluation for PCa with MRI should be a
part of the preprocedure discussion with the patient. A baseline MRI prior to the
UroLift procedure to assess for PCa could also be considered. On MRI following a prior
UroLift procedure, the UroLift device should not be mistaken for other linear metallic
prostate implants utilized in PCa management. Brachytherapy seeds are usually more
numerous than the UroLift tabs with distribution throughout the prostate, unlike UroLift
tabs that are ideally placed anterolaterally at the 10 o'clock and 2 o'clock positions
in the prostate ([Fig. 16]). Fiducial markers used in external beam radiation therapy for PCa are similar in
number to UroLift tabs but are shorter and thicker when compared to UroLift tabs.[43]
Fig. 16 (A) Axial T2-weighted image (T2WI; arrows) shows susceptibility artifacts in the transition zone (TZ) due to the stainless-steel
inner tabs of the UroLift device; outer nitinol tabs are much less conspicuous with
less susceptibility artifacts than inner tabs. (B) Corresponding diffusion-weighted imaging (DWI), (C) apparent diffusion coefficient (ADC) map, and (D) and axial in-phase T1WI show a larger degree of susceptibility artifact, with a
large rounded signal void (arrows) almost obscuring the entire TZ, especially on diffusion imaging. (E) Coronal and (F) axial computed tomography (CT) images better demonstrate the device with inner stainless-steel
tabs (solid arrows) exhibiting relatively greater attenuation than outer nitinol tabs (dashed arrow).
Pitfalls during Staging
-
Assessment of extra-prostatic extension (EPE): EPE assessment is crucial preoperatively due to its association with prognosis after
radical prostatectomy and for deciding whether to spare the neurovascular bundles
at surgery.[44]
[45]
A newly proposed MRI-based EPE grading system showed an accuracy of 77 to 81%.[44]
[46] This is a three-tier system with grade 0 defined as having no suspicion of pathologic
EPE; grade 1 with either capsular contact length (CCL) of ≥15 mm or capsular irregularity/bulge;
grade 2 with both CCL of ≥15 mm and capsular irregularity/bulge; and grade 3 with
frank EPE visible at MRI. Other specific findings of EPE include asymmetry/thickening
of the neurovascular bundle and blunting of the rectoprostatic angle. However, several
pitfalls exist that require careful consideration.
Pearls
A low threshold for suspecting EPE is recommended, particularly at the apex, where
the lack of a capsule poses a higher risk. Apical lesions have implications for radiation
therapy, and are at risk of positive margins and recurrence after radical prostatectomy.
Lesion proximity to the urethra should also be noted since urethral invasion is a
concern (PI-RADS 5) and poses a surgical risk of injury to the external urinary sphincter,
affecting urinary competence ([Fig. 17]).
Fig. 17 (A) Axial T2-weighted image (T2WI) shows a moderately hypointense focal lesion (arrow) in the left apical peripheral zone. The lesion is markedly diffusion restricted
on high b-value (B) diffusion-weighted imaging (DWI; arrow) and (C) apparent diffusion coefficient (ADC) map (arrow), and (D) dynamic contrast enhancement is positive (arrow). Slightly higher (E) axial T2WI (arrow) shows evidence of extraprostatic extension into the posterior periprostatic fat
with asymmetric thickening and (F) enhancement of the left neurovascular bundle (arrow). The lesion involves the prostatic urethra and the external sphincter (arrowheads in A and D). This lesion is thus Prostate Imaging Reporting and Data System 5 (PI-RADS 5).
It should be remembered that MRI underestimates tumor boundaries compared to pathology,[47] with DCE performing better than T2WI and DWI for tumor volume estimation.
T2WI is key for evaluating a seminal vesicle (SV) that typically demonstrates a high
signal on T2WI when distended with seminal fluid. SV invasion, either as tumor growth
along the SV or extension from the prostate base, defines the T3b TNM stage. Tumor
infiltration or focal tumor deposits exhibit T2 hypointensity.[48] However, caution must be exercised as nondistended SV (such as from recent ejaculation)
or benign pathologies, including inflammation and related amyloidosis,[49] can falsely mimic invasion on T2WI due to a dark signal ([Fig. 18A–E]). Corresponding diffusion restriction and focal enhancement can increase confidence
in characterizing T2 signal abnormality as pathologic ([Fig. 18F–J]).
Fig. 18 (A) Axial (arrows) and (B) coronal T2-weighted images (T2WIs; arrows) demonstrate diffuse T2 hypointensity of the seminal vesicles in this patient with
Gleason 3 + 3 disease in the peripheral zone (PZ; not shown). The appearance of the
seminal vesicles is characteristic of amyloidosis, which was noted on a prior prostate
biopsy. Note the (C) absence of enhancement (arrows) and (D,E) diffusion restriction (arrows) in the region of seminal vesicle signal abnormality. In contrast, in a different
patient, (F) axial (arrow) and (G) coronal T2WI (arrow) show irregular T2 hypointense regions within the right greater than the left seminal
vesicles. There are corresponding areas of (H) enhancement (arrow) and (I,J) diffusion restriction (arrow) concerning seminal vesicle extension in this biopsy-proven Gleason 5 + 4 disease
involving the bilateral prostate base (not shown).
-
Lymph node assessment: Pelvic lymph node dissection (PLND) is the most reliable method for documenting
nodal invasion.[50] Prostate MRI allows pelvic and retroperitoneal lymph node evaluation for metastatic
involvement but relies solely on morphological features. A common criterion for identifying
metastatic pelvic nodes is a short-axis diameter greater than 0.8 cm. A meta-analysis
utilizing size criteria of short-axis diameter greater than 1 cm for oval and greater
than 0.8 cm for round nodes with cross-sectional imaging demonstrated a pooled sensitivity
of around 39 to 42% and a specificity of 82% for detecting positive nodes.[51] Nevertheless, metastatic and benign reactive lymph nodes show significant overlap
in size ([Fig. 19]).
Fig. 19 (A) Apparent diffusion coefficient (ADC) map (arrow) shows markedly diffusion restricting Prostate Imaging Reporting and Data System
5 (PI-RADS 5) lesion in the left peripheral zone (PZ) with biopsy showing Gleason
4 + 5 adenocarcinoma. (B) Axial T2-weighted image (T2WI; arrow) and (C) contrast-enhanced T1WI (arrow) show a 0.4-cm rounded perirectal lymph node, which, although not suspicious by the
magnetic resonance (MR) size criteria, was suspicious for (D) metastasis on prostate-specific membrane antigen (PSMA; piflufolastat F-18) positron
emission tomography (PET; arrow).
Pearls
Other morphological signs of malignancy may be helpful, including irregular borders
indicating extranodal extension, a round or irregular shape, and the absence of a
fatty hilum.[52] A combination of morphological criteria and a DWI sequence demonstrated a specificity
of 94% and sensitivity of 41% for detecting lymph node metastasis.[53] While malignant nodes may exhibit lower ADC values than benign nodes, overlap of
their ADC values limits clinical utility.[54]
-
Bone assessment: Bone is the second most common site of early metastases after lymph nodes.[55] Traditional bone scans have limited sensitivity and a high FN rate of up to 40%.
Whole-body MRI with DWI has demonstrated greater accuracy than bone scans in detecting
bone metastases.[56] Routine prostate MRI can also effectively detect bone metastases,[57] given that most PCa metastases arise within the pelvis and lumbar spine, often covered
on prostate MRI.
Pearls
Bone metastases exhibit hypointensity on T1WI, intermediate- to hypointensity on T2WI,
hyperintensity on DWI, and early, robust enhancement on DCE ([Fig. 20]). MRI should be interpreted in the context of the PSA, Gleason score, and clinical
stage to enhance metastatic detection and avoid unnecessary investigation of benign
bone lesions, including hyperplastic hematopoietic bone marrow islands.[58] The presence of intralesional fat is associated with benignity and can be helpful.
Prostate MRI assessment of bone metastases is limited by restricted coverage and varying
image acquisition protocols compared to musculoskeletal MRI (e.g., noninclusion of
short tau inversion recovery [STIR] on mpMRI of the prostate). Depending on the institutional
protocol, bone lesions may often need to be primarily addressed in the large field-of-view
T1WI, while T2WI, DWI, and DCE sequences concentrate on the prostate and SVs for optimal
anatomical detail.[59]
Fig. 20 (A) Axial and (B) coronal T2-weighted (T2W) images show a hypointense focal marrow replacing lesion
involving the left acetabulum (arrow). (C) On T1WI (arrow), the lesion exhibits homogenous hypointensity to a greater degree than adjacent
skeletal muscles. The lesion also exhibits strong enhancement on (D) the postcontrast image (arrow) and (E) diffusion restriction on diffusion-weighted imaging (DWI; arrow) and (F) apparent diffusion coefficient (ADC) map (arrow), which is highly suspicious for metastasis.
