Multiparametric-MRI is an important tool in the diagnosis of prostate cancer (PCa), particularly diffusion-weighted imaging for peripheral zone (PZ) cancer in the untreated prostate. However, there are many benign entities that demonstrate diffusion restriction in the PZ mimicking PCa resulting in diagnostic challenges. Fortunately, these benign entities usually have unique MR features that may help to distinguish them from PCa. The purpose of this pictorial review is to discuss benign entities with diffusion restriction in the PZ and to emphasize the key MR features of these entities that may help to differentiate them from PCa.
Prostate Cancer Diffusion restriction Multiparametric-MRI Prostatitis Hypertrophic nodule Displaced central zone Post-biopsy hemorrhage Granulomatous prostatitis
Prostate cancer (PCa) is the most frequently diagnosed form of non-cutaneous malignant tumor in men and the second leading cause of cancer death in men . It is estimated that one in six men will be diagnosed with prostate cancer in their lifetime . Current clinical screening methods such as prostate-specific antigen (PSA) testing or trans-rectal ultrasound (TRUS)-guided prostate biopsies for PCa lack sensitivity and specificity [3, 4]. In recent years, multiparametric-MRI (mp-MRI) has emerged as an important tool in the diagnosis of PCa and as a means in assisting targeted biopsy, risk stratification, and treatment selection . These advancements in mp-MRI are mainly attributed to the addition of diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE) to the routine prostate MR protocol . However, a wide variety of normal and abnormal entities with diffusion restriction in the peripheral zone (PZ) can mimic PCa on mp-MRI and create diagnostic challenges [6, 7].
The adoption of Prostate Imaging Reporting and Data System (PI-RADS) has been instrumental in promoting a greater level of standardization and consistency with regards to the acquisition, interpretation, and reporting of prostate mp-MRI examinations . According to PI-RADS v2, the dominant sequence for detection of PCa in the PZ is DWI-ADC map. This statement has gained a lot of support from experienced prostate MRI readers, although it is important to keep in mind that many mimics may have falsely high PI-RADS scores because of their diffusion restriction.
Since our department performs MRI-guided and US/MRI fusion-guided prostate biopsies, we have gained extensive experience in differentiating benign from malignant foci that demonstrate diffusion restriction in the PZ. Benign entities with diffusion restriction in the PZ include but are not limited to chronic prostatitis, hypertrophic nodule in the PZ, normal displaced central zone, insertion of capsule and fascia at the midline of the PZ, post-biopsy hemorrhage, thickened surgical capsule, enlarged neurovascular bundle, granulomatous prostatitis, ejaculatory ducts, and prominent periprostatic fat. Recognition of the MR findings of these benign entities that demonstrate diffusion restriction in the PZ, along with the key MR features that may help to differentiate them from PCa, is important in avoiding unnecessary interventions and guiding clinical management.
Prostate cancer in the peripheral zone
PCa in the PZ typically manifests as a hypointense signal focus on T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) map with early contrast wash-in and wash-out on dynamic contrast-enhanced imaging (DCE) (Fig. 1) . At times, PCa may result in mass effect on the adjacent normal prostate tissue and prostate capsule. The ADC value correlates with the PCa Gleason score such that a lower ADC value is usually associated with higher Gleason scores [8, 9]. Diffusion restriction within a lesion raises suspicion for PCa (Fig. 1B) [10, 11]. Typically, an early and avidly enhancing lesion that exhibits >20% rapid wash-out of contrast during the 4-min time interval after intravenous contrast administration will be red on most available DCE images after software processing (Fig. 1C) , raising the suspicion for PCa. If an area in the prostate does not exhibit wash-out, it will be blue in color. A green area in the prostate after software processing indicates wash-out of contrast between 0% and 20%. If an institution does not have DCE as part of its routine protocol, the diagnostic accuracy of PCa may still be maintained, particularly for experienced prostate MRI readers, even though DCE may increase the sensitivity and specificity for the diagnosis of PCa.
Chronic prostatitis is one of the most common benign entities that mimic PCa in the PZ. It may be diffuse or focal in the PZ with hypointense T2 signal, diffusion restriction, and abnormal enhancement, mimicking PCa (Fig. 2) [12, 13]. Despite the overlap of these MR characteristics with PCa, there are clues that help differentiate chronic prostatitis from PCa. On T2WI, the hypointense T2 signal areas in chronic prostatitis are usually geographic, ill-defined, and lack the contour deformity or mass effect on the adjacent normal prostate tissue or capsule that is sometimes seen with PCa . On DCE, these areas may show bilateral symmetric rapid contrast wash-in and wash-out usually in a band-like or wedge-shaped morphology . Most importantly, the degree of diffusion restriction of chronic prostatitis is often less than that seen in PCa, providing crucial evidence that this is not PCa (Fig. 2B) [13, 14].
Hypertrophic nodule in the peripheral zone
Hypertrophic nodules in the PZ have hypointense T2 signal, diffusion restriction, and rapid contrast wash-in and wash-out, mimicking PCa (Fig. 3) . However, these nodules are usually less than 1 cm in size and rounded or oval in shape with discrete, well-defined margins and with thin T2 hypointense encapsulation . Since most of these nodules arise from the transitional zone, they are often continuous with the adjacent transitional zone in one of three planes on T2WI, which provides strong MR imaging evidence of a benign nodule . Hypertrophic nodules usually do not extend to the capsule on T2WI, so that normal tissue between the lesion and the capsule is more often seen as compared to that in PCa (Fig. 3A) [14, 16].
Normal displaced central zone
Current zonal anatomy of the prostate describes three distinct glandular regions: peripheral zone, transition zone, and central zone. The central zone appears as a symmetric band of tissue between the peripheral and transition zones, extending posterior to the transition zone and urethra, proximal to the verumontanum, and surrounding the ejaculatory ducts [17, 18]. The central zone exhibits homogenously hypointense T2 signal and low ADC value relative to the PZ. When the transition zone is hypertrophic, it can compress and displace the central zone superiorly and laterally to the base, just inferior to the seminal vesicles . If this process results in asymmetry of the right or left central zone, the displaced central zone can be misinterpreted as PCa (Fig. 4). However, on T2WI, the central zone is often visualized at the level of the ejaculatory ducts with sharp margins (Fig. 4A). Further, the central zone demonstrates no or minimal rapid enhancement with wash-out on DCE (Fig. 4C), in contrast to PCa with rapid wash-in and wash-out .
Insertion of capsule and fascia at the midline of the peripheral zone
A hypointense T2 signal focus at the midline of the peripheral zone at the level of the midgland to apex may occasionally be identified. It is believed that fusion of the prostatic capsule and fascia at this region is responsible for the hypointense T2 signal focus . This midline hypointense T2 signal focus may show diffusion restriction on the ADC map, mimicking PCa (Fig. 5). MRI features including its midline location, concave contour of the prostate at the focus, and lack of dynamic contrast enhancement are the key clues for differentiating this entity from PCa .
Citrate is found in fairly high concentrations in healthy prostate epithelium and prostatic fluid. In addition to its role as a preservative in semen, citrate also functions as an anticoagulant . This property may contribute to the presence of hemorrhage within the PZ for an extended time after prostate biopsy . Specifically, hemorrhage may cause hypointense T2 signal, diffusion restriction, and abnormal contrast enhancement, mimicking PCa (Fig. 6) . Hemorrhage may also obscure underlining tumor [14, 21], thus further complicating the diagnosis. Key clues for differentiating post-biopsy hemorrhage from PCa include mild diffusion restriction on ADC map and hyperintense signal of the area on T1WI [21, 22, 23]. Additionally, due to decreased levels of citrate in PCa, the degree of hemorrhage in discrete PCa is often significantly less than the surrounding benign prostate tissue. This “hemorrhage exclusion sign,” whereby prostate tumors are outlined by extensive surrounding hemorrhage on T1WI, may aid in tumor localization . A post-biopsy delay of at least 6 weeks or longer is recommended before performing a prostate MRI in order to allow enough time for the resorption of blood products [8, 14].
Thickened surgical capsule
In addition to the anatomic capsule of the prostate that surrounds the PZ, a “surgical” capsule surrounding the transition zone has also been described, since it provides a landmark for benign prostatic hypertrophy (BPH) surgery. This structure arises from the embryologic periurethral septum and is composed of fibrous and muscular tissue . Outward pressure from the development of BPH within the transition zone induces proliferation and thickening of this fibromuscular layer between the transitional and peripheral zone. On MRI, the surgical capsule appears as an elongated hypointense T2 signal area with low ADC value mimicking PCa (Fig. 7A, B). However, the classic location of the surgical capsule (between the transitional zone and PZ) with a band-like or elongated shape can serve as a clue to differentiate it from PCa . Further, as the capsule is simply fibromuscular tissue, there is no dynamic contrast enhancement with wash-out on DCE images.
Enlarged neurovascular bundle
The neurovascular bundle (NVB) includes the nervous plexus, arteries, veins, and additional smaller nerve branches that supply the prostate gland. It has classically been viewed as a discrete structure coursing along the posterolateral margin of the prostate near the prostate capsule at approximately the 5- and 7-o’clock positions . The structure exhibits hypointense signal on T2WI and ADC map. Due to the proximity of the NVB to the PZ, the discrete rounded appearance of the NVB may be mistaken for PCa (Fig. 8). Key clues in differentiating the NVB from PCa include its typical location along the outer edge of the prostate capsule and tubular appearance when tracked across multiple consecutive slices [27, 28, 29].
Granulomatous prostatitis is an uncommon benign inflammatory condition that clinically mimics PCa, since it often presents as a firm nodule on digital rectal exam with elevated PSA . On MR imaging, this entity appears as a discrete mass with significant hypointense signal on T2WI and ADC map mimicking PCa (Fig. 9). Additionally, as this is an inflammatory process, there may be associated infiltration of the periprostatic fat, which can appear similar to extraprostatic tumor extension . Currently, histopathologic analysis is the conclusive method in excluding the presence of underlying tumor. However, correlation with clinical history including a rapid, progressive course of disease and prior bacilli Calmette–Guérin (BCG) immunotherapy is useful when considering granulomatosis prostatitis as a diagnosis [14, 30]. Another clue in differentiation is that granulomatous prostatitis demonstrates large areas without enhancement due to foci of necrosis within the lesion . In one study, caseating necrosis was identified in 76% of cases of infectious granulomatous prostatitis .
The ejaculatory ducts are paired tubules that originate near the vas deferens behind the prostate and next to the seminal vesicles. They course through the prostate and empty into the prostate urethra at the verumontanum. The ducts are visualized in the medial aspect of the PZ near the midline at the level of the base to midgland. Since the ducts are encased by intermittent bundles of longitudinal fibers, they can present as hypointense signal on T2WI and ADC map, mimicking PCa (Fig. 10) [5, 33]. Their typical location, bilateral, and elongated appearance, and lack of rapid contrast wash-in and wash-out on DCE help in differentiating them from PCa.
Prominent periprostatic fat
One of the shortcomings of diffusion-weighted imaging include susceptibility-induced distortions. Susceptibility effects from chemical shift artifacts caused by periprostatic fat can lead to significant diffusion restriction which mimics PCa (Fig. 11A) . However, unlike PCa, fat will demonstrate hyperintense T1 and T2 signal (Fig. 11B) and will not enhance. Another clue in differentiation is that periprostatic fat is located adjacent to but outside the prostate [5, 27].
Although there have been substantial improvements in the accuracy of MRI for the detection of PCa, achieving optimal accuracy can be hindered by many mimics, which create even more difficulty in interpretation for inexperienced prostate MRI readers. In this article, we have demonstrated that a wide variety of benign entities with diffusion restriction in the PZ can mimic PCa. However, these entities also have their own MR features that help to distinguish them from PCa (Table 1). Ultimately, recognition of the unique MR features of these mimics on mp-MRI, along with additional clues that help to differentiate these entities from PCa, is important in establishing a correct diagnosis and guiding clinical management.
Key MR clues that help in differentiating mimics from prostate cancer
Benign causes of diffusion restriction foci in the PZ
Key clues in differentiation
Ill-defined margins with no contour deformity
Slight diffusion restriction
Sometimes symmetric contrast wash-in and wash-out bilaterally
Hypertrophic nodule in the PZ
Round or oval with well-defined margins
Thin T2 hypointense encapsulation
Often continuous with adjacent transitional zone on T2WI
Layer of normal tissue between nodule and prostate capsule
Normal displaced central zone
Commonly symmetric and well defined
At the level of ejaculatory ducts
No or minimal rapid contrast wash-in and wash-out
Insertion of capsule and fascia at the midline of the PZ
Midline location with concave contour of the prostate at the focus
No rapid contrast wash-in or wash-out
Mild diffusion restriction
Hyperintense T1 signal
“Hemorrhage Exclusion Sign”
Thickened surgical capsule
Band-like or crescentic shape
At the junction of the PZ and transitional zone
No rapid contrast wash-in or wash-out
Enlarged neurovascular bundle
Tubular appearance on at least one plane
Located along outer edge of the prostate capsule
Large areas of non-enhancement due to foci of necrosis within the lesion
Located at the medial aspect of the PZ near the midline from the base to midgland
Vargas HA, Akin O, Franiel T, et al. (2011) Diffusion weighted endorectal MR imaging at 3 T for prostate cancer: tumor detection and assessment of aggressiveness. Radiology 259:775–784CrossRefPubMedPubMedCentralGoogle Scholar
Somford DM, Futterer JJ, Hambrock T, Barentsz JO (2008) Diffusion and perfusion MR imaging of the prostate. Magn Reson Imaging Clin N Am 16:685–695CrossRefPubMedGoogle Scholar
Pucar D, Shukla-Dave A, Hricak H, et al. (2005) Prostate cancer: correlation of MR imaging and MR spectroscopy with pathologic findings after radiation therapy-initial experience. Radiology 236:545–553CrossRefPubMedPubMedCentralGoogle Scholar
Haider MA, Kwast TH, Tanguay J, et al. (2007) Combined T2-weighted and diffusion-weighted MRI for localization of prostate cancer. AJR Am J Roentgenol 189:323–328CrossRefPubMedGoogle Scholar
Hoeks CM, Barentsz JO, Hambrock T, et al. (2011) Prostate cancer: multiparametric MR imaging for detection, localization, and staging. Radiology 261:46–66CrossRefPubMedGoogle Scholar
Franiel T, Ludemann L, Rudolph B, et al. (2008) Evaluation of normal prostate tissue, chronic prostatitis, and prostate cancer by quantitative perfusion analysis using a dynamic contrast-enhanced inversion- prepared dual-contrast gradient echo sequence. Invest Radiol 43:481–487CrossRefPubMedGoogle Scholar
Shukla-Dave A, Hricak H, Eberhardt SC, et al. (2004) Chronic prostatitis: MR imaging and 1H MR spectroscopic imaging findings—initial observations. Radiology 231:717–724CrossRefPubMedGoogle Scholar
Rosenkrantz AB, Taneja SS (2014) Radiologist, be aware: ten pitfalls that confound the interpretation of multiparametric prostate MRI. AJR Am J Roentgenol 202:109–120CrossRefPubMedGoogle Scholar
Park SY, Kim CK, et al. (2014) Diffusion-tensor MRI at 3T: differentiation of central gland prostate cancer from benign prostatic hyperplasia. AJR 202:254–262CrossRefGoogle Scholar
Vargas HA, Akin O, Franiel T, et al. (2012) Normal central zone of the prostate and central zone involvement by prostate cancer: clinical and MR imaging implications. Radiology 262:894–902CrossRefPubMedPubMedCentralGoogle Scholar
Schiebler ML, Tomaszewski JE, Bezzi M, et al. (1989) Prostatic carcinoma and benign prostatic hyperplasia: correlation of high-resolution MR and histopathologic findings. Radiology 172:131–137CrossRefPubMedGoogle Scholar
Kiyoshima K, Yokomizo A, Yoshida T, et al. (2004) Anatomical features of periprostatic tissue and its surroundings: a histological analysis of 79 radical retropubic prostatectomy specimens. J Clin Oncol 34:463–468Google Scholar
White S, Hricak H, Forstner R, et al. (1995) Prostate cancer: effect of postbiopsy hemorrhage on interpretation of MR images. Radiology 195:385–390CrossRefPubMedGoogle Scholar
Tamada T, Sone T, Jo Y, et al. (2008) Prostate cancer: relationships between postbiopsy hemorrhage and tumor detectability at MR diagnosis. Radiology 248:531–539CrossRefPubMedGoogle Scholar
Rosenkrantz AB, Kopec M, Kong X, et al. (2010) Prostate cancer vs. post-biopsy hemorrhage: diagnosis with T2- and diffusion-weighted imaging. J Magn Reson Imaging 31:1387–1394CrossRefPubMedGoogle Scholar
Barrett T, Vargas HA, Akin O, Goldman DA, Hricak H (2012) Value of the hemorrhage exclusion sign on T1-weighted prostate MR images for the detection of prostate cancer. Radiology 263:751–757CrossRefPubMedPubMedCentralGoogle Scholar
Phillips ME, Kressel HY, Spritzer CE, et al. (1987) Normal prostate and adjacent structures: MR imaging at 1.5 T. Radiology 164:381–385CrossRefPubMedGoogle Scholar
Nunes LW, Schiebler MS, Rauschning W, et al. (1995) The normal prostate and periprostatic structures: correlation between MR images made with an endorectal coil and cadaveric microtome sections. AJR 164:923–927CrossRefPubMedGoogle Scholar
Poon PY, Bronskill MJ, Poon CS, et al. (1991) Identification of the periprostatic venous plexus by MR imaging. J Comput Assist Tomogr 15:265–268CrossRefPubMedGoogle Scholar
Tempany CM, Rahmouni AD, et al. (1991) Invasion of the neurovascular bundle by prostate cancer: evaluation with MR imaging. Radiology 181:107–112CrossRefPubMedGoogle Scholar
Mohan H, Bal A, Punia RP, Bawa AS (2005) Granulomatous prostatitis: an infrequent diagnosis. Int J Urol 12:474–478CrossRefPubMedGoogle Scholar
Bour L, Schull A, Delongchamps NB, et al. (2013) Multiparametric MRI features of granulomatous prostatitis and tubercular prostate abscess. Diagn Interv Imaging 94:84–90CrossRefPubMedGoogle Scholar
Oppenheimer JR, Kahane H, Epstein JI (1997) Granulomatous prostatitis on needle biopsy. Arch Pathol Lab Med 121:724–729PubMedGoogle Scholar
Gray H (1999) The unabridged gray’s anatomy. Philadelphia: Running Press KidsGoogle Scholar
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