Microsoft Word - 17Valentino.docx No conflict of interest declared. 378 Archivio Italiano di Urologia e Andrologia 2014; 86, 4 Presented at 19th National Congress SIEUN, Fermo 2014 ORIGINAL PAPER DOI: 10.4081/aiua.2014.4.378 Incidentally detection of non-palpable testicular nodules at scrotal ultrasound: What is new? Massimo Valentino 1, Michele Bertolotto 2, Pasquale Martino 3, Libero Barozzi 4, Pietro Pavlica 5 1 UO di Radiologia, Ospedale S. Antonio, Tolmezzo, Udine, Italy; 2 Dipartimento di Radiologia, Università di Trieste, Trieste, Italy; 3 UO di Urologia I Universitaria, Università di Bari, Italy; 4 UO di Radiologia, Ospedale Maggiore, Bologna, Italy; 5 GVM Care and Research, Villalba Hospital, Bologna, Italy. Summary The increased use of ultrasound in patients with urological and andrologi- significant role in the characterization of focal lesions in liver, pancreas, spleen and kidneys. Their use in the cal symptoms has given an higher detection of intra-testic- ular nodules. Most of these lesions are hypoechoic and their interpretation is often equivocal. Recently, new ultrasound techniques have been developed alongside of B-mode and color-Doppler ultrasound. Although not completely standardized, contrast-enhanced ultrasound (CEUS) and tissue elastography (TE), added to traditional ultrasonography, can provide useful infor- mation about the correct interpretation of incidentally detected non-palpable testicular nodules. The purpose of this review article is to illustrate these new techniques in the patient management. KEY WORDS: Testicular lesions; Ultrasound; Contrast enhanced ultrasound; Elastography. Submitted 3 October 2014; Accepted 31 October 2014 INTRODUCTION The increased use of ultrasound (US) in patients with uro- logical and andrological symptoms has given an higher detection of intra-testicular nodules. Most of these lesions are hypoechoic and their interpretation is often equivocal (1). The incidence of non-palpable testicular lesions depends on their size. Non-palpable nodules with a diam- eter of 10 mm account for about 0.2-1% of the patients with testicular nodules investigated with US (2-5). Most of these nodules are benign, including Leydig cell tumor as the main lesion. Nevertheless, if US is inconclusive, surgi- cal exploration is the treatment of choice due to possible malignant nature of the nodule (6). By overcoming the limitation of B-mode and color- Doppler ultrasound, new techniques such as contrast- enhanced ultrasound (CEUS) and tissue elastography (TE) were explored for characterizing the testicular nodules in order to select the appropriate treatment. CONTRAST-ENHANCED ULTRASOUND Over the past decade, US contrast agents have gained a testis is not well establish, even if some Authors advo- cated their utility in trauma, infarction, and tumors. US contrast agents are gas-filled microbubbles of small size (less than 10 µm) able to diffuse in the blood allow- ing the visualization of the vascularization of the nod- ules. They are administered intravenously at the dose of 4.8 mL (one vial of contrast agent) followed by 10 mL of saline solution by an antecubital vein. After a mean delay of 20 seconds, the contrast agent reaches the testes giv- ing its vascular map. The nodules can be depicted as hyper-enhancing, hypo-enhancing or non-enhancing masses in comparison with surrounding tissue. Some Authors advocated use of CEUS in the preoperative assessment of testicular lesions with hypervascularity as an important feature in the diagnosis of malignancy (7). Bubbles remain visible for 2-3 minutes after injection, therefore contrast intensity gradually decreases. TISSUE ELASTOGRAPHY Tissue elastography (TE) has been recently introduced for making non-invasive measurements of the mechanical properties of tissue. It is an imaging method of assess- ment for the elasticity of biological tissues (8). It repre- sents a “new way” of palpation, where a portion of tissue is compressed and the degree to which it displaces is assessed. The most common way to displace the tissue is a manual application of a slight longitudinal compres- sion with a conventional probe (so called “strain imag- ing”): the different tissues create different responses according to their specific elastic modulus (9). TE evalu- ates the relative elasticity of different tissues in a selected region of interest by using a fast cross correlation tech- nique and a combined autocorrelation method. It creates an elastogram that is superimposed to the B-mode ultra- sound image of the tissue and updated in real-time. By convention, the elastograms display a colour-coded map of the relative elasticity. The normal testis in color scale elasticity imaging shows homogenous, soft stiff- ness. Focal lesions depicted as hard on elastography are suspicious for malignancy. Some authors found 87.5% 379 Archivio Italiano di Urologia e Andrologia 2014; 86, 4 M. Valentino, M. Bertolotto , P.Martino, L. Barozzi, P. Pavlica sensitivity, 98.2% specificity, 93.3% PPV, 96.4% NPV and 95.8% accuracy in differentiating malignant from benign lesions in 144 nodules/pseudo-nodules using TE (8). They concluded that TE was a very useful technique in assessing small testicular nodules and all types of pseusonodules and could be helpful in deciding the most appropriate clinical approach, allowing in particular con- servative management in selected cases. TESTICULAR ADRENAL RESTS Testicular adrenal rests are benign corticotropin-depend- ent lesions that are often asymptomatic and occur fre- quently in male patients with congenital adrenal hyperpla- sia (CAH) but have also been described in patients with Cushing’s syndrome and Addison’s disease (10). The reported prevalence by sonography however varies between 24% and 94%. Histologically, testicular adrenal rests consist of hyperplastic adrenal cortical tissue origi- nating from aberrant adrenal tissue that descends with the gonads during embryonic migration (11). On sonog- raphy, the testicular adrenal rests mostly appear hypoe- choic although they may be heterogeneous or hypere- Figure 1. Adrenal rest. a) B-mode US shows a hypoechoic nodule with calcifications. b) On color Doppler the nodule appear hypovascular. c) At CEUS the nodule shows to be hyperenhancing in the arterial phase. d) On TE the nodule is soft, similar to the surrounding testis. choic. Calcifications may be present. The adrenal rests are usually bilateral. An important finding in adrenal rests is that vessels coursing through the lesion are not deviated and this is considered an important feature. CEUS shows the nodules to be hyperenhancing in arte- rial phase with isoenhancement in the venous and later phase. On TE the nodules are usually soft, similar to the surrounding testis (Figure 1). SEGMENTAL TESTICULAR INFARCTION Segmental testicular infarction is an uncommon clinical situation. Etiology is largely considered idiopathic, but cases have been described occurring in patients with hyper-coagulability disorders, vasculitides, or following torsion, trauma, infection (12), and iatrogenic vascular injury (13-15). According with Bilagi et al. (1), segmen- tal testicular infarction typically presents as a solitary solid wedge shaped or round area in the testis, hypoe- choic or with mixed echogenicity, with markedly dimin- Figure 2. Segmental testicular infarction. a) B-mode US shows a hypoechoic nodule with mixed echogenicity. b) On color Doppler the vascularity is absent. c) CEUS shows a characteristic with a perilesional rim of enhancement. d) On TE consistency is slightly soft. Incidentally detection of non-palpable testicular nodules at scrotal ultrasound: What is new? 380 Archivio Italiano di Urologia e Andrologia 2014; 86, 4 ished or absent vascularity. Differential diagnosis with a tumor less vascularised than surrounding testicular parenchyma may be problematic in rounded lesions and when vascularity is not completely absent at color Doppler interrogation. CEUS improve characterization showing a non-enhancing lesion formed by ischemic parenchymal lobules. It therefore provided additional information that may be useful to differentiate this non- surgical lesion from hypovascular tumors also in cases with equivocal features at color Doppler interrogation by presence of intralesional color spots. As the nodule is composed of necrotic tissue, on TE segmental testicular infarction is usually soft, although in acute cases consis- tency may be slightly increased due to edema (Figure 2). LEYDIG CELL TUMOR Leydig cell tumor is a relatively uncommon condition that is characterized by focal proliferation of the andro- gen-synthesizing interstitial cells of Leydig (16). Histologically, it is characterized by an increased number of testicular Leydig cells which displace and compress the seminiferous tubules. Leydig cell tumor constitute about 1-3% of all testicular tumors, and it affects males of 22 to 61 years with a mean age of 37 years (17). On B-mode US, Leydig cell tumor commonly appears as an hypoechoic nodule within the testicular parenchyma. The vascularity within the nodules is variable but usual- Figure 3. Leydig cell tumor. a) B-mode US shows a hypoechoic nodule. b) At color Doppler vascularity is present. c) At CEUS the nodule demonstrates early contrast enhancement, more than the normal testis. d) On TE Leydig cell tumor a hard pattern, probably depending on the number of the cells. ly increased. The nodule usually demonstrates early con- trast enhancement at CEUS, more than the normal testis. Wash-out is often rapid. On TE Leydig cell tumor can demonstrate a soft or a hard pattern, depending on the number and in the size of the Leydig cells, lymphatic or vascular invasion, cytonuclear atypia, number of mitoses, absence of well-defined edge or a capsule (Figure 3). SEMINOMA Classic seminomas histologically are usually homoge- neously solid, lobulated masses that may contain sharply circumscribed areas of necrosis. Microscopically, tumor cells are uniform with abundant clear cytoplasm charac- teristically arranged in nests outlined by fibrous bands; in 80% of cases, these bands are infiltrated by lympho- cytes and plasma cells, possibly due to a host reaction to the tumor (18). The imaging features of seminomas reflect their histologic characteristics and their uniform cellular nature. On US, seminoma is a homogeneously Figure 4. Seminoma. a) B-mode US shows a hypoechoic rounded lesion. b) At color Doppler the lesion appears hypovascular. c) CEUS shows a rapid enhancement of the lesion. d) On TE the nodule is hard. M. Valentino, M. Bertolotto , P.Martino, L. Barozzi, P. Pavlica 381 Archivio Italiano di Urologia e Andrologia 2014; 86, 4 hypoechoic rounded lesion; it may be lobulated or multinodular appearance. Cystic-like spaces are uncom- mon. Seminoma is usually hypervascular at color Doppler interrogation. CEUS shows a rapid enhance- ment of the lesion with an abnormal depiction of cross- ing vessel within the nodule. There is a rapid wash-out but a persistence of the crossing vessels sign. On TE the nodule is usually hard, on occasion, with soft intrale- sional areas due to necrotic changes (Figure 4). NONSEMINOMATOUS GERM CELL TUMORS This is a large group of histologically heterogeneous neo- plasms. Four basic types can be recognized: embryonal carcinoma, teratoma, choriocarcinoma, and yolk sac tumor. The combination of two or more types of these neoplasms results in mixed GCTs. Embryonal carcinoma has a more variable appearance than seminoma. It is mainly a solid tumor containing foci of hemorrhage and necrosis. Teratoma is predominantly cystic and multiloc- ulated. All types of tissues can be seen within the tumor, most commonly fat, cartilage and various types of epithelium. These tumors are further divided into mature and immature teratomas and those with malig- nant areas. Choriocarcinoma represents the most lethal form of testicular carcinomas. This tumor is often small, usually hemorrhagic, and partially necrotic. Yolk sac tumor has a soft consistency and a microcystic appear- Figure 5. Teratoma. a) B-mode US shows a hypoechoic not homogeneous nodule. b) At color Doppler vascularity is poor. c) CEUS demonstrates some bubbles within the nodule suggesting the malignancy. d) On TE the nodule appears clearly hard ance. Therefore, nonseminomatous testicular tumors are expected to appear as hypoechoic not homogeneous masses on US, with anechoic areas of necrosis and hyper- echoic areas of calcification. Increased vascularity may or may not be demonstrated. However, CEUS is more able to demonstrate the vascularity of the nodule, sometimes with rare microbubbles within the lesion suggesting the malignancy. On TE these nodules appear clearly hard (Figure 5). CONCLUSION US is the imaging modality of choice for scrotal patholo- gies. Opposite to palpable testicular masses, non-palpable incidental testicular nodules are often benign and an accu- rate diagnosis is relevant for the appropriate treatment. Advanced and innovative US technology allows a better characterization of small testicular nodules. CEUS and TE are a useful adjunct to traditional B-mode and color- Doppler examination, clearly identifying vascularization and consistency of the nodule. 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