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Contents

Introduction . . . 476

Neoplasms . . . 476

Cyst . . . 476

Definition . . . 476

Pathology . . . 476

Radiologic Findings . . . 476

Hemangioma . . . 478

Pathology . . . 478

Lymphangioma . . . 480

Pathology . . . 481

Hamartoma . . . 481

Pathology . . . 481

Hemangiopericytoma . . . 481

Pathology . . . 482

Epithelioid Vascular Tumor . . . 482

Pathology . . . 482

Littoral Cell Angioma . . . 483

Pathology . . . 483

Lymphoma . . . 483

Pathology . . . 483

Angiosarcoma . . . 486

Pathology . . . 486

Metastases . . . 486

Pathology . . . 486

Infectious Disorders . . . 487

Bacterial Abscess . . . 487

Pathology . . . 488

Fungal Infection . . . 489

Pathology . . . 489

Tuberculosis . . . 490

Pathology . . . 490

Echinococciasis . . . 490

Pathology . . . 491

Pneumocystis carinii . . . 491

Pathology . . . 491

Cat-scratch Disease . . . 492

Pathology . . . 492

Systemic Disorders . . . 492

Collagen Vascular Diseases . . . 492

Pathology . . . 492

Storage Diseases . . . 493

Pathology . . . 493

Sarcoidosis . . . 495

Pathology . . . 495

Hematologic Disorders . . . 496

Sickle Cell Disease . . . 496

Pathology . . . 496

Thalassemia . . . 496

Pathology . . . 496

Acquired Hemolytic Anemia . . . 497

Pathology . . . 497

Idiopathic Thrombocytopenic Purpura . . . 497

Pathology . . . 497

Polycythemia Vera . . . 497

Pathology . . . 497

Myelogenous Leukemia . . . 498

Pathology . . . 498

Myelofibrosis . . . 498

Pathology . . . 498

Spleen

Enrica Segatto, Koenraad J. Mortele, Pablo R. Ros

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Introduction

The spleen is generally not considered a challenge to the radiologist and it is also true that the spleen is an uncommon site of primary disease; however, it may be involved by a variety of different diseases including gen- eralized hematopoietic and lymphopoietic disorders, systemic infections, neoplasms, and immunologic-inflammatory disorders. Some of these conditions have no clinical significance but familiarity with their existence is nevertheless important in order to avoid inter- pretative pitfalls. Computer tomography and ultraso- nography are screening modalities for the spleen. For problem solving, magnetic resonance imaging may be helpful, especially given its free choice of the imaging plane and because of the high contrast resolution. The purpose of this chapter is to present a review of imaging findings of a vast array of splenic diseases, correlated with underlying gross and microscopic pathologic features.

Neoplasms Cyst Definition

Cysts of the spleen may be divided into primary (or true) cysts, which possess a cellular lining, and secondary (or false) cysts, which are without a cellular lining [1]. Primary cysts are either parasitic (echinococcal) or nonparasitic (epithelial). Parasitic cysts, most common in endemic areas where the spleen is affected in less then 5% of cases, are caused by infection with Echino- coccus granulosus [2]. Nonparasitic epithelial-lined cysts of the spleen (typically epidermoid) account for 10%–25% of all cystic lesions and may be a manifesta- tion of a genetic defect of mesothelial migration [3].

Non-epithelial-lined cysts are thought to be secondary to traumatic splenic injuries, and it is reported that they arise from encapsulation of subcapsular or intrasplenic hematomas [4]. They can also result from prior infarc- tions or infections.

Pathology

At histopathologic analysis, echinococcal cyst (parasitic) is composed of three layers: (1) the outer pericyst, which corresponds to compressed and fibrosed splenic tissue; (2) the endocyst, an inner germinal layer; and (3) the ectocyst, a translucent thin interleaved membrane.

Maturation of a cyst is characterized by the development of daughter cysts in the periphery as a result of endocyst invagination. Peripheral calcifications are not uncommon in viable or nonviable cysts [5].

True, nonparasitic (epidermoid) cysts are distinguished from false cysts by their epithelial lining and may have following possible causes, including 1) peritoneal mesothelium infolded after rupture of the splenic capsule, 2) aggregates of peritoneal mesothelial cells trapped in splenic sulci, or (3) dilatation of normal lymphatic spaces [4] (Fig. 1).

Secondary or false cysts tend to have a smoother surface with fibrous tissue lining. They presumably are the residua of previous trauma, splenic infarction or infection. The contents of the cysts can be serous, hemorrhagic, or inflammatory [6, 7].

Radiologic Findings

Sonographically, splenic cysts are anechoic lesions with well-defined walls and increased transmission [8]. Epi- dermoid cysts may appear as anechoic cystic lesions or may have low-level internal echoes and good through transmission. False cysts usually are reported to be ane-

Castleman’s Disease . . . 498

Pathology . . . 498

Vascular Pathology . . . 498

Splenic Vein Thrombosis . . . 498

Pathology . . . 499

Splenic Artery Aneurysm . . . 499

Pathology . . . 499

Splenic Arteriovenous Fistula . . . 499

Pathophysiology . . . 499

Splenic Infarction . . . 501

Pathology . . . 501

Peliosis of the Spleen . . . 501

Pathology . . . 501

Trauma . . . 501

Splenic Injury in Abdominal Trauma . . . 502

Pathophysiology . . . 502

Conclusion . . . 503

References . . . 503

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Fig. 1A–H.Splenic cyst.ATrue cyst. T2-weighted axial MR image shows a large, well-defined cystic mass, arising from the spleen.B Heavily T2-weighted coronal image confirms the cystic nature of the lesion.CContrast-enhanced T1-weighted image shows lack of enhancement of the lesion.DGross specimen clearly demonstrates the unilocular, trabeculated structure of the true cyst.EPhotomi-

crograph of the wall of the cyst shows the epithelial lining, characteristic for the true cysts.FFalse cyst. Ultrasound image shows complex cystic lesion in the spleen with curvilinear peripheral calcifications.GContrast-enhanced CT shows a rounded, low-density lesion, with parietal calcifications.HGross specimen confirms the smoother surface with fibrous tissue lining typical of the false cyst.

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choic; in 15% of cases they show a mixed pattern with solid components and anechoic spaces. Intracystic hemorrhage or debris from inflammation is responsible for the internal echogenicity within the mass [7, 9].

On CT, both true and false cysts appear as thin- walled, unilocular, spherical intrasplenic masses of water density without rim enhancement after contrast material administration (Fig. 1). Cyst wall trabeculation or peripheral septa may be found in either type of cyst, but rim calcification is more common in false cyst. Debris or high-density material may be noted in either type of cyst secondary to intracystic hemorrhage or in the case of false cyst caused by resolving hematoma [4, 10].

MR shows a well-defined, rounded mass with high signal intensity on T2-weighted images and a variable intensity on T1-weighted images depending on the protein or hemorrhagic component of the cystic fluid [11, 12]. Peripheral rim of hypointensity may be caused by the presence of a calcified wall or hemosiderin deposits at the cyst wall.

Hemangioma Definition

Hemangioma is the most common primary benign neoplasm of the spleen and primarily affects adults aged 35–55 years. Hemangiomas are often detected inciden- tally on radiologic or pathologic studies [13]. In Klip- pel-Trenaunay-Weber syndrome, they are often multiple [14].

Pathology

Histologically, hemangiomas are composed of a proliferation of vascular channels of variable size, capillary to cavernous, lined with a single layer of endothelium and filled with red blood cells in an otherwise normal spleen [13] (Fig. 2). Hemangiomas of the spleen may be homogeneously solid or may demonstrate multiple cystic spaces of various sizes within the larger solid tumor mass [13].

On sonography, hemangiomas may appear as discrete echogenic masses with areas of complex echoes, representing blood pools within the proliferating vascular channels or as complex masses with solid and cystic areas [15, 16] (Fig. 2).

On unenhanced CT scans, these lesions may present as homogeneously solid masses (Fig. 2) or as multiple cystic masses [15, 17]. The cystic areas demonstrate a Fig. 1F–H.

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density similar to water and lie within a mass that is iso- dense with normal spleen [15]. Central and punctate or peripheral and curvilinear calcifications may be demonstrated [17]. Peripheral enhancement after intravenous contrast medium administration, with delayed central enhancement, similar to hepatic hemangioma, has been described. In the multicystic type of lesion, the solid portion will enhance following intravenous contrast [15].

On MR examination, splenic hemangiomas typically present low signal intensity on T1-weighted images and higher signal intensity on T2-weighted images, whereas the latter may show heterogeneity representing previous infarction, hemorrhage, or vascular pooling [15, 18]. Dynamic scanning following a rapid bolus of Gd- DTPA may demonstrate three different patterns of enhancement: 1) immediate, homogeneous, persistent enhancement; 2) early peripheral enhancement with uni- Fig. 2A–E.Splenic hemangioma.AUltrasound shows a discrete

echogenic 6-cm mass in the spleen. BUnenhanced CT shows splenic hemangioma as a hypodense partially cystic mass with calcifications.CContrast-enhanced CT image in a patient with he- mangiomatosis shows multiple predominantly cystic lesions in an

enlarged spleen.DGross appearance. Cut section demonstrates a well-circumscribed mass with predominantly solid appearance.

E Photomicrograph of splenic hemangioma shows a vascular channel lined with a single layer of endothelium

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form delayed enhancement; 3) peripheral enhancement with centripetal progression but persistent enhancement of a central fibrous scar [19]. In case of cystic hemangioma, contrast enhancement within the mass may be heterogeneous [20].

Lymphangioma Definition

Lymphangiomas of the spleen are benign neoplasms that are either solitary or multiple (lymphangiomyo-

Fig. 3A–E.Splenic lymphangioma.ASonography demonstrates the typical multicystic appearance of lymphangioma, with the presence of multiple anechoic cysts separated by septations, representing lymphatic spaces.BContrast-enhanced CT scan shows multiple low-density, nonenhancing, thin-walled cysts, which appear, on

MRI (C), markedly hyperintense on T2-weighted images, with hypointense structures representing septations.DGross pathology.

Cut section of specimen demonstrates a multilocular cystic mass.

ELow-power microphotograph demonstrates endothelium-lined cysts

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matosis) [21], usually subcapsular and mostly occurring in childhood. Like hemangiomas, they are also composed of endothelial-lined spaces containing lymph instead of red blood cells [22].

Pathology

Lymphangiomas are usually divided into three types:

capillary, cavernous and cystic, depending on the size of the dilated lymphatic channels. Lymphangioma of the spleen can be of any of the three above-mentioned types [23].

Histologically, lymphangiomas are composed of endothelium-lined cysts of the lymphatic system and classified as capillary, cavernous or cystic depending on the size of the lymphatic channels (Fig. 3). Occasionally the cystic spaces of a lymphangioma contain red blood cells, secondary to hemorrhage. Gross pathology classi- cally shows a unilocular or multilocular cystic mass [24].

On sonography, cystic lymphangiomas usually occur with a multicystic appearance in an enlarged spleen (Fig. 3). The cysts may appear anechoic or hypoechoic.

The presence of internal echoes within cysts depends on the size of the lymphatic spaces and the presence of septa and proteinaceous material [23, 25]. If the cystic spaces are small and below the resolution of the US technique, then portions of the mass may appear hyperechoic due to the existence of numerous reflecting interfaces [23].

CT shows a mass made up of multiple low-density, nonenhancing, sharply marginated, thin-walled cysts, usually subcapsular with or without mural calcifications [26–28] (Fig. 3).After intravenous injection of iod- inated contrast the cystic fluid does not enhance, while the septations present moderate enhancement [23].

On MR, lymphangiomas appear as multiple, well-defined cysts, hypointense on T1-weighted images and markedly hyperintense on T2-weighted images [27], with hypointense internal structures on T2-weighted images, representing septations (Fig. 3). On T1-weighted images, the cysts may rarely be hyperintense, due to the proteinaceous nature of the fluid or internal hemorrhage [23].

Hamartoma Definition

Hamartomas of the spleen are rare benign tumors, clas- sically composed of anomalous mixtures of normal ele- ments of splenic tissue, with red pulp predominating [29]; they may also contain cystic or necrotic components and small calcifications [30] . They are usually less than 3 cm in diameter, but can reach up to 18 cm in size [31] .

Pathology

Histologically, hamartomas are classified into the red pulp (vascular) type, the white pulp (lymphomatous) type, and the mixed type [32]. Grossly, they appear as discrete, circumscribed nodules of various sizes without encapsulation and may be solitary or multiple (Fig. 4).

Splenic hamartomas are usually solid lesions but may have a cystic component [32].

Sonographically, hamartoma may appear as a well-defined, homogeneous, echogenic mass, which may contain cystic areas [32, 33]. In a reported case of splenic hamartoma, gray-scale sonogram showed a hypoechoic, homogeneous splenic mass, whereas color Doppler sonography demonstrated multiple radial blood-flow signals inside the mass, and spectral analysis confirmed arterial and venous flow [34].

On unenhanced CT scan, these tumors may be iso- dense or hypodense and, when they become larger, may show a central area of low attenuation, representing a star-like scar or a region of necrosis with focal calcification (Fig. 4).

MRI demonstrates a well-defined mass, isointense on T1-weighted images, and hypointense to hyperintense on T2-weighted images. After contrast medium administration, both CT and MRI show, on delayed images, more uniform contrast enhancement [20, 35].

Hemangiopericytoma Definition

Hemangiopericytomas are rare vascular tumors appar- ently arising from Zimmerman’s pericytes [36]. They are most frequently described in the muscles of the lower extremities and subcutaneous tissue [37], with a pa- renchymatous origin being extremely infrequent, but especially aggressive [38].

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Pathology

This kind of tumor originates from pericytes. Histolog- ically, hemangiopericytomas consist of numerous capillary channels lined with epithelium and surrounded by and enclosed by nests and masses of spindle cells, which occasionally can be ovoid or even round. Silver impreg- nation can be used to confirm that these cells are out- side the basement of the endothelium and hence are pericytes rather than endothelial cells [39].

On CT scan, reported findings include the presence of a large mass with polylobular contour, along with numerous other smaller lesions disseminated throughout the whole spleen. Hyperattenuation of the solid portions and internal septations after contrast medium administration reflects the vascularity of this tumor [40].

Epithelioid Vascular Tumor Definition

Epithelioid vascular tumors are unusual vascular neoplasms ranging from epithelioid hemangioma (histiocytoid hemangioma, angiolymphoid hyperplasia with eosinophilia) to malignant epithelioid angiosarcoma [41].

Pathology

Epithelioid vascular tumors are characterized by the proliferation of epithelioid (histiocytoid) endothelial cells accompanied by an infiltrate of lymphocytes and eosinophils [41].

Fig. 4A–D.Splenic hamartoma.AArterial phase contrast-enhanced axial CT scan shows a rounded, well-demarcated, splenic mass with a central scar formation.BDelayed-phase contrast-enhanced axial CT scan shows gradual fill in of the lesion with contrast.

CCoronal gadolinium-enhanced MR image shows the heterogeneous enhancement of the lesion during the early phase of splenic enhancement.DCut section of the gross specimen nicely demonstrates the central scar

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Reported radiologic findings are nonspecific and often make the diagnosis difficult, especially when fibrosis, calcification, thrombosis or necrosis is present [42]. On CT, these tumors usually appear as focal, rounded or irregular areas of heterogeneous low attenuation [43]. Oc- casionally, cystic or necrotic portions may be demonstrated. MR may demonstrate a well-defined mass, with heterogeneous texture and hypointense radial streaks representing fibrosis on both T1- and T2-weighted images [42].

Littoral Cell Angioma Definition

Littoral cell angioma is a very rare splenic tumor that arises from splenic sinus-lining cells or littoral cells [44].

Pathology

Grossly, the presence of an enlarged spleen with multiple small nodules is typical. These nodules are histologically characterized by the presence of multiple vascular spaces similar to the venous sinuses of the spleen and covered by high endothelial cells that show hemato- phogocytosis. With the typical littoral cell angioma, no recurrent or metastatic disease is demonstrated [45]. A malignant type, termed littoral cell angiosarcoma, pos- sesses cytologically atypical cells and malignant mor- phologic features, including invasion of surrounding organs [46].

Sonography may demonstrate mainly isoechogenic lesions, with anechogenic foci representing prominent, cavernous blood-filled spaces [47, 48]. Splenomegaly with a mottled echo texture of the spleen, but no presence of discrete focal masses, has also been described [46].

CT scan shows an enlarged spleen containing multiple, ovoid low-attenuation nodular masses [48, 49].

On MR, the lesions show a characteristic signal intensity, hypointense on both T1- and T2-weighted images, which is caused by the presence of hemosiderin in these entities due to the hematophagocytic capacity of the neoplastic cells [47, 50].

Lymphoma Definition

Lymphoma is the most common malignant tumor involving the spleen and may be categorized into primary splenic lymphoma (without evidence of nodal disease) or lymphomatous involvement as a part of disseminated disease [11, 51]. The spleen is involved in approxi- mately 23%–40% of patients with Hodgkin’s disease (HD) or non-Hodgkin lymphoma (NHL) at the time of initial diagnosis [52] .

Although splenomegaly is found in 80% of cases, its presence alone is not a reliable sign of lymphomatous involvement; on the other hand, one-third of normal- sized spleens exhibit tumors in patients with Hodgkin’s disease [2].

Pathology

Four distinct gross pathologic patterns of splenic involvement in lymphoma have been described: 1) homogeneous enlargement without masses; 2) miliary masses (<5 mm in diameter); 3) multiple masses of various sizes (1–10 cm); and 4) a large solitary mass (>5 cm) [53] (Fig. 5). High-grade NHL (e.g., large cell lymphoma) and HD in an advanced stage commonly produce the last two patterns of disease. Lymphocytic lymphomas most likely show a miliary pattern, and low-grade lymphomas typically cause homogeneous involvement [54]. Primary splenic lymphoma usually presents with a mass or masses rather than splenomegaly alone [55].

On ultrasound, splenic lymphoma typically shows a diffuse or focal hypoechoic pattern [56]. Four patterns of involvement have been reported: 1) diffuse heterogeneity (37%); 2) focal, small nodular hypoechoic lesions smaller then 3 cm in diameter (39%); 3) focal, large nodular hypoechoic lesions larger than 3 cm in diameter (23%) (Fig. 5); and 4) bulky mass lesions (2%) [57].

Patients with low-grade HD and NHL commonly present diffuse infiltration of the splenic parenchyma with small nodules. High-grade NHL usually shows focal lesions greater than 3 cm in diameter. Hyperechoic lesions have also been described.

The CT appearance of splenic lymphoma mirrors the variety of pathologic appearances, including 1) homogeneous enlargement without a discrete mass; 2) a solitary mass (Fig. 5); 3) multifocal lesions; and 4) diffuse infiltration [11]. The focal lesions are typically low attenuating and usually range from less than 1 up to 10 cm. The infiltrative pattern and small tumor foci less

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Fig. 5A–F.Splenic lymphoma.AUltrasonography shows a focal large nodular, hypoechoic lesion (pattern type 3).BContrast-enhanced CT demonstrates a focal, low-attenuation lesion in the spleen.CGross pathology. Cut section of specimen shows the large solitary mass appearance of splenic lymphoma.DLow-power mi-

crophotograph demonstrates the presence of lymphatic tumor cells.ET2-weighted images show multiple small nodular hyperintense lesions scattered throughout the spleen.FGross pathology as appears on the corresponding cut section of specimen

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than 1 cm in size may be difficult to detect on CT [58]. It is rare to show a rim of contrast enhancement in lymphoma [59]. Primary splenic lymphoma may be bulky, transgress the splenic capsule and involve adjacent organs such as the diaphragm, stomach, pancreas, and abdominal wall [60]. After intravenous contrast administration, these masses enhance only minimally and appear hypodense with respect to the surrounding spleen

[61]. Calcifications in splenic lymphoma may be occasionally detected, but probably represent dystrophic calcification secondary to hemorrhage, necrosis, and sub- sequent fibrosis [59].

On MR, the T1 and T2 relaxation and proton-density values of lymphoma and normal splenic parenchyma are unfortunately similar [62]. However, by using fast pulse sequences (e.g., double-phase multisection dy-

Fig. 6A–D.Splenic angiosarcoma. A Ultrasound shows a large splenic, discrete echogenic mass.BUnenhanced CT scan shows a focal, poorly defined lesion of low attenuation in the spleen. Note the presence of multiple, similar low-density lesions scattered

throughout the hepatic parenchyma. CA cut section of gross splenic specimen shows multiple hemorrhagic nodules varying in size.DLow-power microphotograph demonstrates vascular channels and sarcomatous stroma

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namic MR imaging) lymphoma may appear clearly as hypointense areas compared with enhanced normal parenchyma [62]. Furthermore, when the lesions are cystic, necrotic or hemorrhagic, they are easier to detect [63] (Fig. 5). Also, use of MR contrast media such as superparamagnetic iron oxide, or AMI-25, has im- proved detection of splenic lymphoma [54].

Angiosarcoma Definition

Angiosarcoma, although exceedingly rare, is the most common primary nonlymphoid vascular malignant tumor of the spleen, with a poor prognosis and early widespread metastases.

Pathology

Angiosarcoma is a malignant neoplasm of vascular origin, characterized by masses of endothelial cells dis- playing cellular atypia and anaplasia.

Grossly, the spleen is enlarged and typically contains multiple hemorrhagic nodules varying in size, frequently associated with hemorrhage, infarction, and necrosis [64]. Microscopically, all degrees of differentiation of these tumors may be found, but two main features have been described: the formation of vascular channels and a sarcomatous stroma [6] (Fig. 6). Various patterns are recognized, including a spindle cell variant, papillary type, and undifferentiated sarcomatous variety; in this more malignant variant, pleomorphism, tumor giant cells, and mitoses are characteristic.

Ultrasound may show a mildly enlarged spleen with multiple hyperechoic masses or a solitary mass with a complex echo pattern [65] (Fig. 6).

CT may demonstrate a diffuse, poorly defined focal mass of heterogeneous or low attenuation in an enlarged spleen with occasional intratumoral necrosis and subcapsular or extracapsular blood collections [40, 66]

(Fig. 6). Areas of high attenuation on unenhanced CT may represent acute hemorrhage or hemosiderin deposits. Contrast enhancement of angiosarcoma may be similar to that of cavernous hemangioma, although the pattern of enhancement is variable, ranging from the presence of multiple low-attenuation masses within the spleen to a mottled nodular enhancing appearance [66].

MRI, on all pulse sequences, may exhibit multiple nodular masses with low signal rims, caused by hemo-

siderin deposition [11]. The signal intensity of central portion on T1-weighted images may vary, depending on the degree of necrosis and hemorrhage [11, 67]. Hyper- intense areas encountered in T1- and T2-weighted images may be considered as regions of subacute hemorrhage [67] . Enhancement of the tumor with gadolinium is intense [66].

Metastases Definition

Splenic metastases are uncommon and occur only in a few percent of patients with widespread malignant disease, usually resulting from hematogenous spread from primary tumors, e.g., in breast, lung, ovary, stomach, prostate, and malignant melanoma [11]. However, solitary splenic metastases have been described, without evidence of involvement of other organs [68].

Pathology

One-third of intrasplenic metastases appear as microscopic nodules, and the other two-thirds are grossly vis- ible at autopsy [69]. Splenic metastases may be solitary (31.5%) (Fig. 7) or multiple (60%) nodular lesions or diffuse infiltrating lesions (8.5%) and can appear as discrete nodules or as confluent tumor masses [70].

Fig. 7A–C.Splenic metastases.AContrast-enhanced CT scan demonstrates a low-attenuating mass in the spleen.BA cut section of the spleen demonstrates a large solitary and heterogeneous lesion.

CPhotomicrograph shows the presence of metastatic cells

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On ultrasound, splenic metastases are predominantly hypoechoic, but may display a mixed or hyperechoic appearance [11]. Larger lesions tend to be more complex than smaller ones, and diffuse involvement of the spleen may be seen in 10% of cases [71].

On CT, splenic metastases typically appear as low-attenuating solid or cystic masses with homogeneous or occasionally heterogeneous contrast enhancement [11]

(Fig. 7).

MRI is accurate to demonstrate splenic metastases with necrosis or hemorrhage, which appear hyperintense on T2-weighted images. Detection of smaller metastases is harder without intravenous contrast medium administration, because they usually have, like lymphoma, the same MR tissue characteristics as the normal splenic parenchyma [63]. The use of ferrumoxides has been shown to improve detection of splenic metastases among patients with widespread malignancy [72].

Infectious Disorders Bacterial Abscess Definition

Splenic pyogenic abscesses are uncommon, with a reported incidence less than 1% in large autopsy series [73]. However, their frequency is growing as a result of an increasing number of immunosuppressed or chroni- cally debilitated patients because of aggressive chemo- therapy regimen, hematological disorders, diabetes, and AIDS [74, 75]. Immunosuppressed patients account for 25% of patients with splenic abscess [76]. The most common pathogens are streptococci, staphylococci and salmonella, but every pyogenic organism may be involved.

Fig. 7B, C.

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Pathology

Histologically, an abscess consists of dead leucocytes (pus) surrounded by a highly vascularized fibrous capsule, the wall of the abscess (Fig. 8).

On US, splenic pyogenic abscesses typically appear as focal hypo- or anechoic lesions or as lesions with a sol-

id and cystic component [77] (Fig. 8). They may also appear similar to cysts, often with a thick and irregular wall, and they may show echoes due to debris, septations or gas bubbles [77]. Gas is uncommon but, if it is present, increased echogenicity combined with “dirty”

shadowing can be demonstrated [22].

CT may show the presence of a focal low-attenuating well-defined lesion, with an attenuation ranging from 20 HU to 40 HU [78]. Minimal peripheral contrast enhancement may be present when a capsule has devel- oped, although it is less common in splenic than in he-

Fig. 8A–D.Splenic pyogenic abscess.ASonography shows a focal hypoechoic lesion in the spleen.BContrast-enhanced CT scan demonstrates the presence of solitary, low-attenuating, well-defined lesion, with minimal peripheral contrast enhancement.

CGross pathology specimen demonstrates the fibrous capsule surrounding abscess cavity.DPhotomicrograph shows the histologic appearance of the wall of the abscess

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patic abscesses (Fig. 8). The presence of gas is usually di- agnostic; unfortunately, only the minority of splenic abscesses contain gas [11, 74]. CT is very sensitive in de- tecting splenic abscesses but is not specific. There are several differential diagnoses, including splenic infarct, cysts, tumors, and hematomas, so fine-needle aspiration may be useful to confirm the diagnosis [79].

At MR imaging, splenic abscesses usually appear as low signal intensity on T1-weighted images, with high signal on T2-weighted images, but may have some low signal representing necrotic debris [80].

Fungal Infection Definition

Fungal abscesses have been reported to account for up to 26% of splenic abscesses [81]. The most common pathogen is Candida albicans, and is usually diagnosed in immunocompromised patients on therapy for leuke- mia. Other fungi include Aspergillus and Cryptococcus fungi.

Pathology

Histologically, concentric rings with central necrotic hyphae can be seen; these rings are surrounded by viable hyphae and a rim of peripheral inflammation [82].

Grossly, the entire spleen may demonstrate multiple small (less than 5 mm in size) fungal deposits (Fig. 9).

Ultrasound may demonstrate the presence of multiple, small, rounded, hypoechoic areas scattered throughout the spleen or a diffusely hypoechoic spleen [83].

Similarly, on CT, multiple small lesions of relatively low attenuation, typically ranging from a few millime- ters to 2 cm in diameter, are seen (Fig. 9). Occasionally, a central area of higher attenuation or a wheel-within-a- wheel pattern may be demonstrated [22].

At MR imaging, splenic fungal abscesses appear as multiple small lesions, which are hypointense on T1- weighted images and hyperintense on T2-weighted images [11] (Fig. 9). The use of fat saturation with T2- weighted images may improve detection of these small lesions, as well as the use of gadolinium [71].

Fig. 9A–D.Candidiasis.AContrast-enhanced CT scan shows multiple, tiny (<1 cm), low-attenuation lesions scattered throughout the spleen.BThe T2-weighted MR image demonstrates the presence of diffuse small hyperintense lesions in the spleen and in the liver.

CGross pathology specimen of the spleen shows multiple, small, white nodules throughout the parenchyma.DLow-power view of splenic specimen shows multiple candidiasis microabscesses, with a peripheral zone of fibrosis and a central area of necrosis

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Tuberculosis Definition

Tuberculosis is a chronic bacterial infection caused by Mycobacterium tuberculosis and characterized by the formation of granulomas in infected tissues and by cell- mediated hypersensitivity. The usual site of disease is the lung, but other organs may be involved. The rate of extrapulmonary involvement increased with the onset of the HIV epidemic [84]. TB of the spleen is extremely common in patients with disseminated disease; however, it is not usually identified at initial presentation [85].

When present, there usually is miliary hepatosplenic dissemination in association with miliary pulmonary TB [86]. Miliary TB may manifest only as mild to moderate splenomegaly [11].

Pathology

Histologically, a TB granuloma consists of giant cells and epithelioid cells and is characterized by a tendency for fibrosis and caseation, a unique form of nonliquefy- ing necrosis [87]. Caseous necrosis of the tubercle be- gins after 2–4 weeks, and fibrous scarring may ensue (tuberculoma).

In the miliary form, US may demonstrate the bright- spleen pattern, consisting of a diffuse increase in echogenicity or the presence of small hypoechoic lesions. On CT, tiny, low-density foci scattered throughout the spleen may be seen (Fig. 10); when the lesions are larg-

er, they may appear as small, focal splenic nodules of low attenuation. Occasionally, small peripheral wedge- shaped areas of low attenuation may be present, which represent infarcts from septic emboli [87].

In the macronodular form, occurring less commonly, US may demonstrate the presence of round and hypoechoic areas. On CT, the disease appears as a diffuse spleen enlargement containing multiple, low-density, 1- to 3-cm round lesions or a single mass. This feature may evolve to an abscess with single or multiple low-density, septate, or honeycomb-like lesions. These lesions have irregular, ill-defined margins, and show, after intravenous contrast medium administration, minimal or slight central enhancement. With further evolution of the disease, the lesion typically appears as an abscess with single or multiple low densities with ring-like enhancement [88]. MRI may demonstrate a hypointense lesion with a less hypointense rim on T1-weighted images, which appears hyperintense with a less hyperintense rim on T2-weighted images.

Echinococciasis Definition

Splenic infection by Echinococcus is uncommon and is usually associated with liver and/or lung involvement;

Echinococcus is the only parasite to produce splenic cysts [71]. The most common organism is Echinococcus granulosus; less commonly, hydatid disease is caused by Echinococcus multilocularis. The cysts, solitary or mul- tiple, may cause a focal mass effect or splenic enlargement and they may demonstrate aspecific, peripheral, ring-like calcification [71].

Fig. 10.Tuberculosis. Contrast-enhanced CT scan shows multiple, small, low-density lesions throughout the spleen

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Pathology

Histologically, an Echinococcus cyst appears as a three- layered structure consisting of the inner germinal layer, the endocyst of hyaline and the pericyst, which is a thin band of vascularized, fibrotic compressed spleen (Fig. 11). Daughter cysts develop from germinal layers and are responsible for the multilocular form on gross

pathologic examination. Scolices and fragments of the germinal layer constitute the so-called hydatid sand within the cyst [87].

On sonography, anechoic lesions with daughter cysts and calcifications or occasionally a solid mass with fine internal echoes, representing debris, infolded mem- branes, scolices, or hydatid sand, may be seen [89]. Sep- aration of the membrane produces a pathognomonic appearance for hydatid disease: the water-lily sign, resulting from the detachment and collapse of the inner germinal layer from the ectocyst. The collapsed germinal layer is seen as an undulating, linear collection of echoes either floating in the cyst or lying in the most de- pendent portion [90].

Unenhanced CT is sensitive in depicting subtle cyst wall calcifications [22]. The CT attenuation of the cyst depends on intracystic content, which usually shows water attenuation values. The presence of debris, hydatid sand and inflammatory cells may determine high CT values [91]. No enhancement is seen after the administration of contrast material, except for the possible ring- like enhancement of the external cyst wall and the enhancement of the internal trabeculae [92] (Fig. 11).

On MRI, typically a well-defined, rounded mass with signal intensity of water is seen on both T1- and T2- weighted sequences. The presence of protein or hemorrhage content in the cystic fluid may vary the signal intensity on T1-weighted images, whereas signal intensity on T2 images remains quite high [11]. The presence of a hypointense rim on T1-weighted and T2-weighted images, corresponding to wall calcification, and a multi- loculated appearance are considered to be distinctive features of this lesion [93].

Pneumocystis carinii Definition

Pneumocystis carinii infection is becoming more com- mon with the increasing prevalence of an immunosuppressed population, and there is an increasing incidence of extrapulmonary disease. This infection affects 80% of patients with AIDS and is one of the major causes of morbidity and mortality [94].

Pathology

Histologically, splenic P. carinii infection causes necro- tizing granulomas that eventually develop dystrophic calcification within the granulomas [94].

Fig. 11A, B.Echinococciasis.AContrast-enhanced CT scan shows a round, low attenuating, cystic splenic mass with discontinuous rim calcifications. B Gross pathology of splenic specimen demonstrates the three-layered structure of the echinococcal cyst

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In the early phase of the disease process, US typically shows tiny, highly reflective, nonshadowing foci and small hypoechoic lesions with cystic components. In later stages, calcification develops and acoustic shadowing is seen [95].

On CT, there is mild splenomegaly, and the spleen presents multiple low-attenuation lesions, which may enlarge and become progressively calcified in either a rim-like or a punctate fashion [11].

Cat-scratch Disease Definition

Cat-scratch disease is an infection that usually affects children and adolescents after being scratched by a do- mestic cat [96] and it has been attributed to Bartonella henselae. The patient typically has had intimate expo- sure to a cat and presents with unilateral regional lym- phadenitis and a site of inoculation.

Pathology

The lesions of the spleen may be distinguished in one or two distinct types on the basis of the histopathologic findings: vascular proliferative lesions (bacillary peliosis splenitis) or necrotizing granulomatous lesions [97].

Sonographically, splenic granulomata generally appear as hypoechoic lesions, ranging from well defined and homogeneous to indistinct and heterogeneous; enhanced through-transmission may occur [98]. On CT, multiple scattered areas of low attenuation, ranging from 3 mm to 2 cm in size, in the spleen may be seen [96]. On MRI, the lesions appear hypointense on T1- weighted images and hyperintense on T2-weighted images [99]. Resolution of the lesions detected on imaging may take 4–6 weeks.

Systemic Disorders Collagen Vascular Diseases Definition

Collagen vascular diseases include a group of disorders of immune regulation, which, therefore, may involve the spleen, since it is an organ of the immune system. The

function and structure of the spleen can be affected through lymphoid hyperplasia in the white-pulp area and through dysfunction of phagocytic red-pulp areas, which are responsible for the destruction of cells. This red-pulp dysfunction results from autoimmune cyto- penias [100]. The most important collagen vascular diseases include: rheumatoid arthritis (RA) and Felty’s syndrome, systemic lupus erythematosus, Wegener’s granulomatosis and polyarteritis nodosa.

Rheumatoid arthritis (RA) is a chronic multisystem disease of unknown origin, characterized by persistent inflammatory synovitis of peripheral joints in a sym- metric distribution and by variable extra-articular manifestations. Felty’s syndrome consists of a triad of chronic RA, splenomegaly, neutropenia, and, occasionally, anemia and thrombocytopenia [101]. It occurs preferentially in the fifth to seventh decade of life and after long-standing RA (of more than 10 years); 70% of Felty’s syndrome patients are female [100].

Systemic lupus erythematosus (SLE) is a multi- systemic disease of unknown etiology in which tissues and cells are damaged by pathogenic autoantibodies and immune complexes, occurring in 90% of cases in women [102]. The spleen is involved in 15%–45% of patients; splenomegaly and lymphadenopathy are the most commonly reported findings. Possible complica- tions are splenic infarction, spontaneous splenic rupture, functional asplenia and hyposplenia [100].

Wegener’s granulomatosis is also a systemic disease of unknown origin, characterized by a clinicopatholog- ic complex of necrotizing granulomatous vasculitis of the upper and lower respiratory tract, glomeruloneph- ritis and variable degrees of vasculitis of small arteries and veins. The disease can affect any organ and system.

Splenic involvement, however, generally is considered to be rare [103].

Polyarteritis nodosa (PAN) is a systemic inflammatory disease that causes a necrotizing vasculitis of medium-sized arteries and is also characterized by aneurysm formation [104].

Pathology

In Felty’s syndrome, the enlargement of the spleen is caused by expansion of the red pulp and sinuses, which contain many macrophages [105].

Systemic lupus erythematosus is characterized, histologically, by the presence of large-and small-vessel necrotizing vasculitis with an onion-skin pattern.

In Wegener’s granulomatosis, grossly, a central area of infarction surrounded by a red peripheral zone of splenic parenchyma has been reported [103]. Microscopical- ly, granulomatous vasculitis of small and medium-sized arteries and veins, with thrombotic occlusion and hemorrhage, which causes infarction, may be seen [106].

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In Polyarteritis nodosa, similarly to Wegener’s granulomatosis, a necrotizing vasculitis of medium-sizes arteries may be seen; the disease is also characterized by aneurysm formation [104].

Generally, in rheumatoid arthritis (RA), Felty’s syndrome, and systemic lupus erythematosus, all the different imaging modalities (US, CT, and MRI) may be used to assess the presence of splenomegaly, splenic calcification, and splenic atrophy or for detection of com- plications such as rupture or splenic abscess [100].

In Wegener’s granulomatosis, ultrasound may show a heterogeneous parenchymal architecture [107] or multiple hypoechoic intrasplenic nodules [108], with paten- cy of the splenic artery and veins [107]. On CT, a diffuse pattern of splenic infarction has been reported in addi- tion to a pattern of rim enhancement around a large central area of low attenuation [103]. MRI may demonstrate the presence of diffuse low signal intensity on T1- weighted images and high signal intensity on T2- weighted images, which represent the diffuse infarction pattern [109].

In polyarteritis nodosa, ultrasound and CT scans may be useful in the detection of splenic rupture or abscess formation [100].

Storage Diseases Definition

In storage diseases, splenic dysfunction and anatomic distortion are the result of deposition of abnormal sub- stances into the reticuloendothelial system (red-pulp area). The most common storage disorders involving the spleen are: Gaucher’s disease, Niemann-Pick disease, Langerhans cell histiocytosis, amyloidosis, and iron-overload diseases.

Gaucher’s disease is a metabolic disorder in which glucocerebroside accumulates in the reticuloendothelial system because of a deficit of the enzyme glucocere- brosidase and is characterized by the presence of focal nodules in different organ systems. The disease most often follows a chronic, progressive course, characterized by hepatosplenomegaly, anemia, thrombocytopenia, and erosion of the endosteum of long bones [1].

Niemann-Pick disease consists of a group of recessive autosomal diseases that are clinically and biochem- ically heterogeneous [110]. The basic defect is a disorder of sphingomyelin metabolism, leading to lipid deposition in certain organs such as brain, liver, and spleen.

Four clinical forms of Niemann-Pick disease have been described by Schubert [111] on the basis of differences

in the age of onset and the presence of neurological symptoms.

Langerhans cell histiocytosis (LCH) is a rare disorder of the bone-marrow-derived histiocytes, which may manifest in a single-system disease or in a multisystem- ic disorder [100]. Many organs may be affected, including bone, skin, bone marrow, liver, spleen, lungs, lymph nodes, pancreas, intestine, brain, pituitary gland, and buccal involvement.

Amyloidosis is the deposition of eosinophilic proteinaceous material (amyloid substance) in different organs. Splenic involvement is common, as the cells of the reticuloendothelial system play a major role in the formation of amyloid [112].

Iron-overload diseases consist of two different groups of disorders, depending on the location of iron deposition [113]. Primary hemochromatosis is a common inherited autosomal recessive disorder, consisting of abnormal parenchymal iron deposition, which occurs mainly in the hepatocytes but also in the pancreas, heart and synovium [100]. This parenchymal iron deposition may cause damage and organ dysfunction such as cirrhosis of the liver and development of hepatocellu- lar carcinoma. Hemosiderosis is the term used for iron deposition in the reticuloendothelial system of the liver, spleen, lymph nodes and bone marrow; it most commonly develops after multiple blood transfusions (transfusional iron overload) and has little clinical significance [1].

Pathology

Gaucher’s disease is pathologically characterized by the presence of focal nodules consisting of focal homogeneous clusters of Gaucher’s cells (reticuloendothelial cells laden with glucocerebroside) and fibrosis or infarction [114].

In Niemann-Pick disease, the metabolic defect leads to the storage of lipids (sphingomyelin and cholesterol) in the histiocytes. These multivacuolated, lipid-laden cells (or foam cells) are mainly found in the reticuloendothelial system of the spleen and the liver, the lymph nodes, bone marrow and lungs. In certain types of the disease, they are also found in the central nervous system.

Langerhans cell histiocytosis of the spleen is characterized, histologically, by a diffuse splenic red-pulp infiltration by Langerhans cells, with the typical Birbeck granule within their cytoplasm on electron microscopic examination. Grossly, splenomegaly and splenic rupture have been described, and less commonly, the presence of a solitary nodular lesion [115].

Splenic amyloidosis is pathologically characterized by the presence of amyloid deposits in the splenic parenchyma and in the splenic vasculature [116].

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Histologic features of the spleen in iron-overload diseases are iron deposition in the reticuloendothelial system in hemosiderosis and splenomegaly in association with symptomatic liver involvement in hemochromatosis [100].

In Gaucher’s disease, ultrasound, CT, and MR studies show marked splenomegaly and the resultant mass effect on adjacent structures. Ultrasound may also reveal multiple discrete hypoechoic lesions or hyperechoic lesions, depending on different histopathologic features of the nodules [100]. Aspestrand et al. [117] reported a case with multiple hypoechoic lesions surrounded by hyperechoic rims (the target appearance). CT may show multiple hypodense lesions, which, after intravenous contrast material administration, enhance to a lesser degree than the surrounding splenic parenchyma [118, 119] (Fig. 12). On MR, the spleen may demonstrate in-

creased signal intensity on T1-weighted images as a result of shortening of the T1 relaxation time, which seems to result from accumulation of glucocerebroside in the spleen [120] (Fig. 12). The presence of splenic nodules, with variable signal intensity and variable size has also been described [121, 122]. Most splenic nodules are isointense on T1-weighted images and hypointense on T2-weighted images, while some lesions are hyperintense on T2-weighted images. A minority of lesions are hyperintense on T1-weighted images.

In Niemann-Pick Disease, ultrasound may show nodular splenomegaly with multiple, well-defined hy- perechogenic nodules, which appear hypodense on a contrast-enhanced CT scan, probably due to the dimin- ished blood flow [110]. On MR, a diffuse increase in signal intensity of the spleen on T1-weighted images and on T2-weighted-images has been reported, probably caused by the lipid infiltration of the splenic parenchyma. The presence of nodular lesions within the spleen, isointense on T1-weighted images and hyperintense on T2-weighted images has also been described [110].

Few cases of imaging findings of Langerhans cell his- tiocytosis have been reported. On sonography, the pres- ence of multiple, round, hypoechoic lesions of varying sizes in an enlarged spleen have been described [123], as also a case of a solitary hypoechoic lesion within the spleen [124].

Cross-sectional imaging is rarely performed in patients with amyloidosis of the spleen, because most patients have no clinical symptoms related to splenic amyloid infiltration. No characteristic features that distin- guish amyloidosis from other infiltrative disorders have been reported. Rarely, extensive visceral calcifications involving both the liver and the spleen have been described in primary amyloidosis [125]. Sonography and emergency CT may also be useful to confirm hemoper- itoneum and an enlarged heterogeneous spleen in cases of acute splenic rupture [100].

In iron-overload diseases, CT shows diffuse in- creased attenuation values in the liver [1]. However, this finding is not specific and very insensitive for moderate degrees of iron deposition [100]. MRI is a more sensitive and a specific method to detect iron deposition because of the magnetic-susceptibility effect caused by the accumulated iron. This demonstrates a markedly decreased signal intensity (compared with that seen in skeletal muscle) in involved organs on T2-weighted images, especially on T2*-weighted gradient-echo images.

In hemochromatosis, a low signal intensity on T2- and T2*-weighted images is found in the liver, pancreas, myocardium and endocrine glands, but the spleen remains normal [126]. In hemosiderosis, spleen, liver and bone marrow reveal decreased intensity on MR studies and the pancreas tends to be spared [1].

Fig. 12A, B.Gaucher’s disease.AContrast-enhanced CT scan demonstrates a subcapsular, wedge-shaped, low-density area, in an enlarged spleen.BOn MRI the spleen shows increased signal intensity. Note the presence of splenic hypointense nodules