Genitourinary Schisto- Somiasis: Life Cycle and Radiologic-Pathologic Findings1

Home , Genitourinary system, Seminal vesicles, Urinary bladder

Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights. GENITOURINARY IMAGING 1031 Genitourinary Schisto- somiasis: Life Cycle and Radiologic-Pathologic Findings1

Haytham M. Shebel, MD • Khaled M. Elsayes, MD • Heba M. Abou El ONLINE-ONLY CME Atta, MBBCh, PhD • Yehia M. Elguindy, MBBCh • Tarek A. El-Diasty, MD See www.rsna .org/education Genitourinary schistosomiasis is produced by Schistosoma haemato- /rg_cme.html bium, a species of fluke that is endemic to Africa and the Middle East, and causes substantial morbidity and mortality in those regions. It also LEARNING may be seen elsewhere, as a result of travel or immigration. S haemato- OBJECTIVES bium, one of the five fluke species that account for most human cases After completing this of schistosomiasis, is the only species that infects the genitourinary journal-based CME activity, participants system, where it may lead to a wide spectrum of clinical symptoms will be able to: and signs. In the early stages, it primarily involves the bladder and ure- ■■Describe the pathogenesis of ters; later, the kidneys and genital organs are involved. It rarely infects genitourinary schis- the colon or lungs. A definitive diagnosis of genitourinary schistoso- tosomiasis. miasis is based on findings of parasite ova at microscopic urinalysis. ■■Recognize the clinical manifestations of Clinical manifestations and radiologic imaging features also may be genitourinary schis- suggestive of the disease, even at an early stage: Hematuria, dysuria, tosomiasis. and hemospermia, early clinical signs of an established S haematobium ■■Identify imaging features suggestive infection, appear within 3 months after infection. At imaging, fine ure- or indicative of geni- teral calcifications that appear as a line or parallel lines on abdomino- tourinary schistosomiasis. pelvic radiographs and as a circular pattern on axial images from computed tomography (CT) are considered pathognomonic of early-stage schistosomiasis. Ureteritis, pyelitis, and cystitis cystica, conditions that are characterized by air bubble–like filling defects representing ova deposited in the ureter, kidney, and bladder, respectively, may be seen at intravenous urography, intravenous ureteropyelography, and CT urography. Coarse calcification, fibrosis, and strictures are signs of chronic or late-stage schistosomiasis. Such changes may be especially severe in the bladder, creating a predisposition to squamous cell carcinoma. Genital involvement, which occurs more often in men than in women, predominantly affects the prostate and seminal vesicles.

©RSNA, 2012 • radiographics.rsna.org

RadioGraphics 2012; 32:1031–1046 • Published online 10.1148/rg.324115162 • Content Codes:

1From the Department of Radiology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt (H.M.S., H.M.A., T.A.E.); and De- partment of Radiology, University of Texas M.D. Anderson Cancer Center, 1400 Pressler St, Houston, TX 77030 (K.M.E., Y.M.E.). Presented as an education exhibit at the 2010 RSNA Annual Meeting. Received September 16, 2011; revision requested October 12 and received December 20; ac- cepted January 10, 2012. For this journal-based CME activity, the authors, editor, and reviewers have no relevant relationships to disclose. Address correspondence to K.M.E. (e-mail: [email protected]).

©RSNA, 2012 1032 July-August 2012 radiographics.rsna.org

Introduction Two major forms of schistosomiasis exist: in- Schistosomiasis, one of the most protean diseases testinal and genitourinary. Intestinal schistosomi- in humans, was known to the pharaohs more asis may be caused by any of five main species of than 5000 years ago. The presence of snail spe- blood flukes (Table). However, onlySchistosoma cies in the Paleolithic Age in Africa may indicate haematobium affects the genitourinary system (5). an even older history for this parasitic disease. S haematobium is endemic throughout Africa, The ancient Egyptians recognized schistosomiasis Madagascar, Mauritius, the southern shore of the as a cause of bloody urine and stools and knew Mediterranean, and the Middle East, including that the condition was due to worms (1). Turkey. It primarily involves the urinary tract and In 1851, Theodor Bilharz described this para- the hepatic portal system, but it may also affect sitic infection, which consequently became known the colon and lungs (1,4,6). as bilharziasis but was later renamed schistosomiasis. Schistosomiasis (also known as “snail fever”) Life Cycle of S Haematobium is a complex of parasitic infections that are caused The life cycle of S haematobium consists of two by various trematodes of the genus Schistosoma, main stages, one of which is completed in fresh- whose first hosts are aquatic or amphibious snail water snails, and the other, in humans and other species that live in fresh water. Humans and other mammals (Fig 1). mammals may be infected through contact with water containing the parasites. Schistosomiasis is First Stage: Freshwater Snails a major source of morbidity and mortality in the The life cycle of S haematobium begins when eggs developing countries of Africa, South America, the of the parasite excreted by a mammal host reach Caribbean, the Middle East, and Asia; however, fresh water, where they hatch and release mira- tourism to and immigration from endemic areas cidia. The free-swimming miracidia can survive may lead to occurrences of the disease anywhere 1–3 weeks in fresh water. During this time, the in the world (2,3). miracidia must infect a snail of the genus Bulinus In 1996, the World Health Organization (4) es- in order to complete their life cycle. These snails timated that more than 200 million people world- may be found in slow-moving freshwater streams, wide were affected by schistosomiasis, mainly irrigation ditches, or nearly any other open water those living in rural agricultural and periurban source (natural or artificial) in endemic regions. areas. Of that number, it was estimated that 20 In the snail, the miracidium develops into an million were severely affected by the disease and adult sporocyst, from which thousands of larval that another 120 million were symptomatic. cercariae are released 4–6 weeks after the initial According to the World Health Organization, infection (7,8). The cercariae, fork-tailed free- schistosomiasis is one of the most widespread hu- swimming larvae approximately 1 mm in length, man parasitic infections, ranking second to malaria can survive only 72 hours in fresh water. During in terms of its effects on the socioeconomic status that time, they must either attach themselves to and health of populations living in tropical and and penetrate the skin of humans or other sus- subtropical regions. It is considered to be the most ceptible host mammals or die. Cercariae also may prevalent waterborne disease and a major occupa- enter a human or other mammal host by pen- tional health risk in rural areas of developing coun- etrating the buccal mucous membrane; however, tries, where it results primarily from the unsanitary cercariae that are swallowed are digested in the disposal of human and animal wastes, combined stomach (9–12). with repeated daily contact of people with contam- inated freshwater sources (eg, in fishing, farming, Second Stage: swimming, bathing, and recreation) (5). Humans and Other Mammals After penetrating the skin of the human or mam- Epidemiologic Character- mal host, the larvae shed their tails and become istics and Forms of Schistosomiasis schistosomula. The schistosomula enter the lym- Schistosomiasis is prevalent in tropical and sub- phatic system and pass through the thoracic duct tropical regions, especially in poor communities into the right side of the heart. They then travel with no access to safe drinking water or adequate through the lungs to the left side of the heart and sanitation. Of the 207 million people with schis- proceed along the mesenteric capillaries to the tosomiasis, 85% live in Africa (1,4). hepatic portal system and liver, where they mature and copulate. This journey takes 10–21 days. They then migrate along the endothelium, against the RG • Volume 32 Number 4 Shebel et al 1033

Figure 1. Schema shows the two-stage life cycle of S haematobium.

Geographic Distribution of Schistosoma Species That Infect Humans

Species by Targeted Body System Endemic Countries and Geographic Regions Intestinal tract S mansoni Africa, Middle East, Caribbean, Brazil, Venezuela, Suriname S japonicum China, Indonesia, Philippines S mekongi Several districts of Cambodia, Laos S intercalatum Rain forests of central Africa S guineensis Rain forests of central Africa Genitourinary system S haematobium Africa, Middle East

portal blood flow, to the vesicular venous plexus, wall and are shed in urine or feces. During this which envelops the lower part of the bladder and migration, which takes approximately 10 days, the base of the prostate; there, they produce eggs. miracidia develop inside the eggs. Eggs that are Maturation of the parasite also may occur in other not shed successfully may remain in the host’s organs, especially the lungs, but copulation outside tissues, where they soon become nonviable, or the liver is uncommon (8,13). may be swept back from the mesenteric vessels The eggs are highly antigenic and may induce to the portal circulation or from the vesicular an intense granulomatous response in human vessels via the inferior vena cava to the pulmo- hosts. After their excretion by the mature para- nary circulation (14). site, the eggs migrate through the host’s bladder 1034 July-August 2012 radiographics.rsna.org

Figure 2. Photomicrograph (original magnification, ×200; hematoxylin-eosin stain) shows a fresh ovum from S haematobium, floating in a human urine specimen. Figure 3. Photomicrograph (original magnification, Note the terminal spine at one end of the ovum. ×100; hematoxylin-eosin stain) of a histologic slice from the bladder wall of a patient with schistosomiasis shows a granuloma with multiple calcified ova at its center, Clinical Manifestations surrounded by a zone of reactive inflammatory tissue Clinical manifestations reflect the parasite’s containing giant cells. developmental stage and the host’s response to toxic or antigenic effects of the parasite and its eggs. During the early stage of infection, the patient may present with dermatitis caused by cercarial penetration of the skin (15). This self- limited process may recur more intensely with subsequent exposures to the same species. Cer- carial dermatitis may be followed by broncho- pulmonary manifestations that are attributed to the passage of schistosomula through the lungs (16–18). Approximately 5 weeks after infection, a condition known as Katayama disease may develop; this condition is characterized by marked clinical manifestations such as malaise, weight loss, gastrointestinal symptoms, eosinophilia, and Figure 4. Photomicrograph (original magnification, fever. However, Katayama disease is uncommon ×100; hematoxylin-eosin stain) shows multiple calcified ova of S haematobium with surrounding reactive inflam- in people infected initially by S haematobium and matory tissue in the submucosa of the bladder. is more likely to occur in those who are reinfected (19,20). The stage of egg deposition is manifested by genitourinary symptoms of cystitis, dysuria turia are common in both early and late stages with terminal hematuria, dull suprapubic pain, of disease. Proteinuria, often with values that are and hemospermia. In women, it also may be in the nephrotic range, may be a late manifesta- manifested by hypertrophic, ulcerative, fistulous, tion. Definitive diagnosis is based on findings of or wartlike vulval and perineal lesions that may ova at microscopic analysis of urine specimens be mistaken for another type of infectious geni- (4,21) (Fig 2). tal lesion, particularly condylomata lata due to syphilis. Tubal infertility may be a late complica- Histopathologic Findings tion. Vulval schistosomiasis also may facilitate the Adult schistosomes do not usually cause an transmission of human immunodeficiency virus. inflammatory reaction in the venous system. Hematuria, the first clinical sign of estab- In fact, their presence there is associated with lished genitourinary schistosomiasis, appears increased protection of the host against reinfec- 10–12 weeks after infection. Dysuria and hema- tion by cercariae. In general, dead eggs and dead flukes cause a more severe inflammatory reaction than living ones do (22). RG • Volume 32 Number 4 Shebel et al 1035

Figure 5. Ureteral lesions due to S haematobium infection. (a) Photograph shows a gross ureteral specimen that contains multiple mural projections. (b) Photomicrograph (original magnification, ×200; hematoxylin-eosin stain) of a slice obtained from the specimen in a shows many cystic lesions lined with multiple layers of low cuboidal cells.

structures (Fig 5). These structures differentiate into cystic deposits of cystitis cystica or intestinal columnar mucin-secreting glands, resulting in cystitis glandularis, which may develop into adenocarcinoma. Cystitis cystica, ureteritis cystica, and cystitis glandularis can be observed as polypoid filling defects on radiographs.In long- standing infections, a cellular reaction to dead Pathologic changes in the urinary tract due to ova produces calcification and fibrosis, which are schistosomiasis are far more common in chronic important contributors to squamous metaplasia infections than in acute ones. Such changes result and squamous cell carcinoma (25,26). from the deposition of eggs (not adult flukes) Severe fibrosis classically involves the bladder in and around vessels, which leads to chronic and ureteral segments distal to the iliac vessels inflammatory lesions and induces an immune re- (hereafter referred to as “distal ureters”), dimin- sponse with granuloma formation and associated ishing their elasticity. Severely fibrotic ureters have fibrotic changes (23). a ragged outline and a beaded internal appearance, The deposition of eggs in the bladder and with irregular dilatation due to pseudotubercles in ureter induces a chronic granulomatous reaction the submucosa. As the pseudotubercles heal, they (Fig 3). The disease usually starts at the urinary may become fibrotic, a condition that may lead to bladder trigone and base, with the formation of ureteral stricture. Renal involvement in late-stage submucosal granulomas leading to inflammatory fibrosis, which usually results from vesicoureteral patches and hematuria. Cystitis resembling that reflux, is manifested by renal calculi and hydro- in tuberculosis results in “sandy patches” on the nephrosis or pyonephrosis secondary to ureteral bladder wall that, in severe cases, may become a obstruction. Urethral involvement usually occurs network of dense concentric calcifications (4,24) in the form of fossa navicularis polyps, periurethral (Fig 4). The degree of calcification is roughly cor- abscesses, and perineal and scrotal fistulas; stric- related with the number of eggs deposited. tures are uncommon (27). Chronic irritation of the urothelium causes it to proliferate, producing budlike or polypoid 1036 July-August 2012 radiographics.rsna.org

Figures 6, 7. (6) Excretory urogram demonstrates bilateral distal ureteral dilatation secondary to early-stage urinary tract infection by S haematobium. (7) Urinary tract schistosomiasis. (a) Excretory urogram shows substantial dilatation of the distal left ureter, likely a result of ureteral narrowing at the level of the pelvic bone. (b) Postmicturition radiograph shows persistent filling of the left ureter with a nondi- lated right ureter.

Schistosomal infection of the prostate gland the prostate, followed by fibrosis and shrinkage and seminal vesicles is found at autopsy in 58% with calcification of the gland. The seminal vesi- of male cadavers in geographic regions where S cles may become enlarged and calcified. Ejacu- haematobium is endemic. The epididymis, sper- latory duct dilatation may result from distal matic cord, and testes are rarely affected. Pros- fibrosis and obstruction. Genital schistosomiasis tatic involvement leads to initial enlargement of is not as common in women as in men, but lesions may be found in the vulva, vagina, and cervix, and more rarely in the ovaries, fallopian tubes, and uterus (28,29). RG • Volume 32 Number 4 Shebel et al 1037

Figure 8. Urinary tract schistosomiasis. (a) Excretory urogram shows marked left hydroureteronephrosis. (b) Coronal three-dimensional urographic image obtained with computed tomography (CT) shows a long-segment stricture with proximal dilatation of the left ureter.

Imaging Findings The peristaltic movement of the ureter is af- Radiologic imaging manifestations of urinary fected by two main factors: ureteral stricture due tract schistosomiasis are observed mainly in the to fibrosis, and mural calcification that begins ureters and bladder. The kidneys appear normal in the bladder wall. Fibrosis of the ureteral wall until a late stage of disease. and periureteral tissue affects the nerve plexus of the ureter, causing hypotonia mainly in the Ureters distal ureteral segment; peristalsis in the proximal Ureteral involvement in schistosomiasis has been ureteral segment (the segment between the ure- reported in as many as 65% of cases (30,31). The teropelvic junction and the iliac vessels) is normal earliest change visible at urography is persistent until the advanced stage of fibrosis, in which the filling of the distal ureteral segment of the ureter, whole ureter is involved (31,34,35). Once blad- followed by distal ureteral dilatation (Figs 6, 7). der calcification has occurred, peristalsis in the Early-stage ureteral dilatation results from ureteral distal ureteral segment decreases to half the nor- dysfunction, not tissue damage; is generally uni- mal rate. When the distal one-third of the ureter lateral; and ranges from slight to severe. At a later becomes dilated and calcified, normal peristalsis stage, ureteral fibrosis resulting from tissue healing may still continue in the proximal ureter. When may lead to ureteral strictures. More than 80% of no normal peristalsis is present in the distal ure- the earliest ureteral strictures occur in the intra- teral segment, reverse peristalsis may occur. As vesical segment of the ureter (ie, the part within calcification extends up the ureter, peristalsis the bladder); the second most common location is gradually decreases. By the time hydronephrosis 2–5 cm (1–2 inches) above the orifice. The part of and hydroureter have developed, peristaltic activ- the ureter affected by fibrosis extends above and ity has usually ceased (31,36). below the stenotic ureteral segment. As fibrosis Fine ureteral calcification may be observed at progresses, the entire length of the ureter may be an early stage of schistosomiasis, initially with ar- involved, with multiple strictures (32,33) (Fig 8). eas of sparing but eventually coalescing until the entire length of the ureter is calcified, from the 1038 July-August 2012 radiographics.rsna.org

Figure 9. Urinary tract schistosomiasis. (a, b) Negative (a) and positive (b) anteroposterior radiographs show thin calcification of the bladder wall and the entire length of the left ureter (arrows ina ). (c) Unenhanced axial pelvic CT image more clearly depicts the bladder wall calcification.(d) Sagittal reformatted CT image more clearly shows the distal left ureteral calcification (arrow). bladder to the kidney. The fine ureteral calcifica- Bladder tion is visible as a linear or parallel linear pattern In the early stages of schistosomal infection, the on radiographs and as a circular pattern on axial bladder outline becomes hazy and ill defined at CT images. These radiologic imaging findings are urography because of submucosal edema and considered pathognomonic (30,34) (Fig 9). pseudotubercles. The bladder wall becomes thick- Ureteritis cystica and pyelitis cystica, which ened and ulcerated with multiple small flat papil- are characterized by air bubble–like filling de- lomas that can be distinguished from a malignancy fects in the ureter and renal pelvis, respectively, at cystoscopy and bladder biopsy (38–40). also may be seen at intravenous urography, in- Schistosomiasis-induced changes in the blad- travenous ureteropyelography, and CT urogra- der vary widely, depending on the geographic re- phy (37) (Figs 10, 11). gion. In Egypt, a syndrome called “bladder neck obstruction” has been described; the condition is relatively common and results from eggs entering RG • Volume 32 Number 4 Shebel et al 1039

Figures 10, 11. (10a) Excretory urogram obtained in a 46-year-old woman shows multiple filling defects along the course of the distal left ureter (arrows). These findings represent ureteritis cystica due to schistosomiasis. (10b) Postmicturition radiograph shows multiple filling defects in the bladder, findings indicative of cystitis cystica due to schistosomiasis. The T-shaped object is an intrauterine contraceptive device. (11) Coronal three-dimensional CT urogram obtained in an 83-year-old man with hematuria shows multiple bilateral filling defects along the course of both ureters (arrows). These findings represent ureteritis cystica due to schistosomiasis.

the muscles of the urinary bladder and induc- matobium is endemic; it accounts for as many as ing partial hyperplasia that evolves into fibrosis. 56% of cases of such calcification (30,44). Bladder The trigone is the bladder region most severely wall calcification is due to the presence of a large affected by hypertrophy, which involves the for- number of calcified dead eggs in the submucosa. mation of a prominent bulge between the ureteral The degree of calcification is roughly correlated orifices that protrudes into the bladder lumen. with the number of calcified eggs but not with As the hypertrophic tissue undergoes fibrosis, it the number of eggs discharged in urine, which atrophies and shrinks, leaving the mucosa and depends on the activity of the parasite. A region muscularis as a mass that is pushed forward over containing as few as 100,000 calcified eggs per the internal urethral orifice, leading to obstruc- cubic milliliter can be detected at radiography. The tion at the level of the bladder neck. Such marked number of eggs required to produce an amount bladder outlet changes have not been reported of calcification detectable at CT is not known; outside Egypt (41–43). however, calcification becomes detectable when Schistosomiasis is the most common cause of attenuation exceeds 160 HU (30). At radiography, bladder wall calcification in regions whereS hae- 1040 July-August 2012 radiographics.rsna.org

Figure 12. Extensive bladder calcifications due to late-stage schistosomiasis.(a) Pelvic radiograph shows the classic appearance of the calcified bladder, which resembles a fetal head in the pelvis, with associated faint calcification of the distal right ureter (arrows).(b) Axial pelvic CT image shows thick calcification of an extensive region of the bladder wall and ringlike calcification of the wall of both ureters, with patent ureteral lumina. (c) Axial pelvic CT image obtained in another patient shows a completely calcified bladder wall and calcifications obstructing both ureteral lumina.

bladder calcifications are visible first at the bladder base, forming a linear pattern that parallels the upper border of the pubic bone; eventually, calcium deposits encircle the entire bladder (44). The classic presentation of a calcified bladder, which resembles a fetal head in the pelvis, is pathognomonic of chronic urinary tract schistosomiasis (Fig 12). Various calcification patterns have been reported, depending on the state of bladder filling: In the empty bladder, calcifications appear coarser and thicker because the collapsed bladder wall has thick folds. Other patterns that may be submucosa into the bladder and their excre- seen include fine granular, fine linear, and thick -ir tion in the urine. An excretion rate of about regular calcification. Calcification may encircle the 2,000,000 eggs per year is necessary to allow bladder or may affect only parts of it; calcification bladder decalcification. If all calcified eggs are may be more marked on one side than the other, discharged, the bladder wall may return to rela- or more marked at the base than at the vault. A tive normality. Bladder calcification is less com- shell-like rim of calcification, an appearance pro- mon in the elderly than in young people (48). duced by the submucosal deposition of eggs and not caused by fibrosis, has little to no effect on Schistosomal Bladder Masses.—Chronic irritation bladder capacity or emptying. Later in the course of the bladder mucosa leads to an inflammatory of infection, when the bladder wall becomes fi- reaction in the tissue (24). The urothelium prolif- brotic and the bladder contracts, leading to a erates into buds (von Brunn nests), which grow reduction in capacity, marked changes become into the connective tissue beneath the epithelium visible at cystography (37,45–47). in the lamina propria. These buds then differenti- Bladder calcification may resolve partially or ate into cystic deposits leading to cystitis cystica completely because of the reabsorption of calci- (Fig 10b), or intestinal columnar mucin-secreting fied eggs in situ or the rupture of eggs from the glands (goblet cells) producing cystitis glandularis (49,50). Cystitis glandularis and cystitis cystica may occur at any age; the reported prevalence RG • Volume 32 Number 4 Shebel et al 1041

Figure 13. Squamous cell carcinoma of the bladder. (a) Axial T2-weighted magnetic resonance (MR) image shows a soft-tissue mass arising from the left lateral wall of the bladder with multiple small diverticula. (b) Axial T2-weighted MR image at the level of the bladder neck shows extension of the mass through the urinary bladder wall to the perivesical fat with infiltration of the left seminal vesicle.

is 2.4% in children with urinary tract infections, The imaging findings of squamous cell carci- including schistosomal infections (51). At cys- noma in the bladder are nonspecific. A nodular toscopy in patients with either of these forms of or fungating mass is visible on radiologic images cystitis, the mucosa usually has a cobblestone-like in 80% of cases. Tumors may appear as a single appearance. In addition, in late-stage cystitis glan- enhancing mass or as diffuse or focal regions of dularis, a papillary or polypoid mass may arise that bladder wall thickening (55,56). Multiplicity of mimics carcinoma and demonstrates a predilec- tumors is seen in 25% of cases. Squamous cell tion for the bladder neck and trigone (25,26). carcinoma is sessile, not papillary like urothelial cell carcinoma, and purely intraluminal growth is Squamous Cell Carcinoma.—In geographic not seen. Bladder wall thickening and calcifica- regions where schistosomiasis is not endemic, tion due to a coexistent chronic S haematobium squamous cell carcinomas account for less than infection may complicate the diagnosis. Muscle 5% of all bladder malignancies (52). In regions invasion is present in 80% of cases, and extravesi- where schistosomiasis is endemic, it constitutes cal spread may be extensive (56). Tumors are a major risk factor for bladder malignancies, pre- most commonly found in the trigone and lateral dominantly for squamous cell carcinomas, which wall of the bladder but may also arise in bladder account for more than 50% of bladder cancers diverticula (57). At cystoscopy, a squamous cell (53). Chronic S haematobium infection induces carcinoma of the bladder appears as a large, often squamous metaplasia, which may evolve into ulcerated, infiltrating mass that usually spreads squamous cell carcinoma. Among people who do laterally from the mucosa into the bladder wall not have chronic schistosomiasis, squamous cell and surrounding tissues and abdominal wall (Fig carcinomas of the bladder tend to manifest in 13); the usual route of lymphatic spread is via the those older than 60 years, with a slight male pre- paraaortic lymph nodes (58). dominance; patients with chronic schistosomiasis Given the large percentage of patients with and squamous cell carcinoma of the bladder tend extravesical extension at the time of diagnosis, the to be younger and are five times more likely to be overall prognosis for squamous cell carcinoma male. Clinical manifestations of squamous cell of the bladder is generally poor. Two-thirds of carcinoma of the bladder include gross hematuria and irritative voiding symptoms (54). 1042 July-August 2012 radiographics.rsna.org

Figure 14. Left hydroureteronephrosis due to schistosomiasis. (a) Coronal T2-weighted MR urogram shows marked left hydroureteronephrosis with a normal right kidney and right ureter. (b) Axial T2-weighted image depicts dilatation of the left ureter at the level of the bladder. the tumors are poorly differentiated and are di- teral obstruction and vesicoureteral reflux. Renal agnosed at an advanced stage, likely because of disease develops slowly, even in the setting of the similarity between the symptoms of bladder hydronephrosis, hydroureter, and chronic vesico- carcinoma and those of previously diagnosed uri- ureteral reflux. MR urography is the modality of nary tract schistosomiasis. Death usually results choice for assessing the morphologic character- from local extension, with metastases found in istics and function of the urinary tract, especially only 8%–10% of cases. Aggressive local treat- in patients with hydronephrosis and poor kidney ment with radical cystectomy is the treatment function (1,4) (Fig 14). of choice. Given the poor prognosis, physicians should consider performing regular screening Genitals with cytologic urinalysis and cystoscopy in high- Schistosomal infection of the prostate gland and risk patients (59). seminal vesicles has been found at autopsy in as Vesicoureteral reflux may occur as a late many as 58% of male cadavers in regions where complication of schistosomiasis, resulting from S haematobium is endemic (28). This diagnosis fibrosis and ureteral stenosis; it eventually occurs should be considered when calcifications of the in approximately 30% of patients with a substan- prostate gland, seminal vesicles, or bladder wall tially calcified bladder. Voiding cystourethrog- are seen on transrectal ultrasonography (US) or raphy is the examination of choice for detecting CT (Fig 15) in patients presenting with a change vesicoureteral reflux, focal bladder wall thicken- in ejaculate color or quality (eg, a yellow color or ing, large polypoid lesions in the urinary tract, watery consistency), particularly in young men hydroureter, and hydronephrosis (60). who are known to have traveled to or lived in endemic areas (61–63). At US, echogenic foci may Kidneys be visible in the prostate gland, with occasional The kidneys are not the main target of S haema- dilatation of the ejaculatory ducts or seminal tobium, but they may be affected in cases of ure- vesicles because of distal fibrosis and obstruction. In some patients, no changes are apparent at radiologic imaging (28) (Figs 16, 17). RG • Volume 32 Number 4 Shebel et al 1043

Figure 15. Calcification due to schistosomiasis of the seminal vesicles and vasa deferentia. (a) Unenhanced axial CT image shows calcification of both seminal vesicles.(b) Postmicturition radiograph from excretory urography shows calcification of the vasa deferentia and iliac vessels (arrows). (c) Coronal three-dimensional reformatted pelvic CT image shows calcification of both seminal vesicles (arrowheads) and the left vas deferens (arrow).

Figure 16. Transrectal US image of the prostate in a patient with genitourinary schistosomiasis shows a region of dense prostatic calcification that produces an anterior acoustic shadow. 1044 July-August 2012 radiographics.rsna.org

Chronic prostatitis is common in the setting of schistosomiasis and is often associated with seminal vesiculitis (64–66). On MR images, the size and signal intensity of the prostate gland may be normal. However, low signal intensity may be visible in the peripheral zone of the gland on T1- and T2-weighted MR images. This signal intensity ab- normality may be focal or diffuse and is not usually accompanied by deformation of the prostate contour, although it may appear nodular, mimicking prostate carcinoma (67). Seminal vesiculitis is usually seen in the sub- acute or chronic phase of genital schistosomiasis. Vesiculitis appears as diffuse wall thickening of the seminal vesicle, which has low signal intensity on T2-weighted MR images and may demon- strate dilatation, cystic change, atrophy, convolu- tion loss, proteinaceous and hemorrhagic fluid content with variable signal intensity on T1- and T2-weighted images, and surrounding inflammatory changes (68–72). US in patients with vesiculitis usually reveals dilatation and wall thickening Figure 17. Seminal vesiculitis due to schistosomiasis. of both seminal vesicles (Fig 17). The diagnosis (a) Transrectal US image of the seminal vesicles shows bilateral wall thickening (arrows). (b) High-resolution can be definitively established at microscopy with axial T2-weighted MR image of the pelvis shows thick- visualization of S haematobium eggs in seminal ened seminal vesicle walls (arrows). fluid (28,61,73). Schistosomiasis of the testis (also known as bilharzial orchitis) commonly causes testicular be mistaken for manifestations of other genital edema. In some patients, a testicular schistosomal infections, particularly condylomata lata. Vulval granuloma may simulate a mass (74). The schis- schistosomiasis may facilitate the transmission tosomal lesion appears on US images as a solid of human immunodeficiency virus by causing testicular mass with a heterogeneous echotexture thinning, erosion, and ulceration of the cervical or hypoechogenicity and shows increased vascu- epithelium (29,78). larity at color Doppler flow imaging, an appearance identical to that of most testicular malignan- Conclusions cies. Epididymal lesions may simulate neoplasms, Schistosomiasis is a complex of parasitic diseases infarcts, or foci of inflammation (75–77). with varied manifestations caused by different The male genitals are more commonly affected Schistosoma species. Most cases of human schisto- by schistosomiasis than the female genitals. Fal- somiasis are caused by S haematobium, S mansoni, lopian tubes that are infected by S haematobium or S japonicum. Only S haematobium infects the may become blocked, causing an abscess to form, human urinary tract. The article reviews the life but tubal calcification has not been recorded. cycle of S haematobium, the modes of its trans- Cervical edema due to schistosomiasis may re- mission to humans, and the clinical manifesta- semble cervical carcinoma at US, and the two tions and imaging features secondary to its infec- entities may be difficult to differentiate clinically. tion of the urinary tract and genital organs. Although S haematobium may be recovered from the cervix uteri, this finding may not be diagnos- Acknowledgment.—The authors thank David Bier, tically useful, since schistosomiasis and cervical medical illustrator at the University of Texas M. D. Anderson Cancer Center, for providing the schematic carcinoma can coexist. Schistosomiasis has been of the life cycle of S haematobium. implicated in cases of vesicovaginal fistula but is more likely to be a complication than a cause; References schistosome-induced fibrosis also has been shown 1. El Khoby T, Galal N, Fenwick A. The USAID/ to delay fistula healing (15). Vulval and perineal Government of Egypt’s Schistosomiasis Research lesions induced by schistosomiasis may be hyper- Project (SRP). Parasitol Today 1998;14(3):92–96. trophic, ulcerative, fistulous, or wartlike and may 2. Chitsulo L, Engels D, Montresor A, Savioli L. The global status of schistosomiasis and its control. Acta Trop 2000;77(1):41–51. RG • Volume 32 Number 4 Shebel et al 1045

3. Patz JA, Graczyk TK, Geller N, Vittor AY. Effects 24. Grignon DJ, Sakr W. Inflammatory and other condi- of environmental change on emerging parasitic dis- tions that can mimic carcinoma in the urinary blad- eases. Int J Parasitol 2000;30(12-13):1395–1405. der. Pathol Annu 1995;30(Pt 1):95–122. 4. Ross AG, Bartley PB, Sleigh AC, et al. Schistoso- 25. Hochberg DA, Motta J, Brodherson MS. Cystitis miasis. N Engl J Med 2002;346(16):1212–1220. glandularis. Urology 1998;51(1):112–113. 5. World Health Organization. The control of schisto- 26. Lee G, Tsiriopoulos I, Yajnik K, Smith R, Pancharat- somiasis: first report of a WHO expert committee. nam M. Case report: cystitis glandularis mimics Technical Report no. 728. Geneva, Switzerland: bladder tumour—a case report and diagnostic char- World Health Organization, 1985. acteristics. Int Urol Nephrol 2005;37(4):713–715. 6. Woolhouse ME, Taylor P, Matanhire D, Chandi- 27. Hugosson CO, Olsen P. Early ureteric changes in wana SK. Acquired immunity and epidemiology Schistosoma haematobium infection. Clin Radiol of Schistosoma haematobium. Nature 1991;351 1986;37(5):501–503. (6329):757–759. 28. Vilana R, Corachán M, Gascón J, Valls E, Bru C. 7. Wu GY, Halim MH. Schistosomiasis: progress and Schistosomiasis of the male genital tract: trans problems. World J Gastroenterol 2000;6(1):12–19. rectal sonographic findings. J Urol 1997;158(4): 8. Weinstock JV. The pathogenesis of granulomatous 1491–1493. inflammation and organ injury in schistosomiasis: 29. Feldmeier H, Krantz I, Poggensee G. Female geni- interactions between the schistosome ova and the tal schistosomiasis: a neglected risk factor for the host. Immunol Invest 1992;21(5):455–475. transmission of HIV? Trans R Soc Trop Med Hyg 9. Jordan P, Webbe G, Sturrock R. Human schistoso- 1995;89(2):237. miasis. Wallingford, England: CAB, 1993. 30. Jorulf H, Lindstedt E. Urogenital schistosomiasis: 10. Waine GJ, McManus DP. Schistosomiasis vaccine CT evaluation. Radiology 1985;157(3):745–749. development: the current picture. Bioessays 1997;19 31. Umerah BC. Evaluation of the physiological func- (5):435–443. tion of the ureter by fluoroscopy in bilharziasis. 11. Houston S, Kowalewska-Grochowska K, Naik S, Radiology 1977;124(3):645–647. McKean J, Johnson ES, Warren K. First report of 32. Abdel-Wahab MF, Ramzy I, Esmat G, el Kafass Schistosoma mekongi infection with brain involve- H, Strickland GT. Ultrasound for detecting Schis- ment. Clin Infect Dis 2004;38(1):e1–e6. tosoma haematobium urinary tract complications: 12. Sturrock RF. The schistosomes and their intermedi- comparison with radiographic procedures. J Urol ate hosts. In: Mahmood AAF, ed. Schistosomiasis. 1992;148(2 Pt 1):346–350. London, England: Imperial College, 2001; 7–83. 33. Abdel-Halim RE, Al-Mashad S, Al-Dabbagh A. 13. Abdel-Wahab MF, Esmat G, Ramzy I, et al. Schis- Fluoroscopic assessment of bilharzial ureteropathy. tosoma haematobium infection in Egyptian school- Clin Radiol 1985;36(1):89–94. children: demonstration of both hepatic and urinary 34. Young SW, Khalid KH, Farid Z, Mahmoud AH. tract morbidity by ultrasonography. Trans R Soc Urinary-tract lesions of Schistosoma haematobium Trop Med Hyg 1992;86(4):406–409. with detailed radiographic consideration of the ure- 14. Corachan M. Schistosomiasis and international ter. Radiology 1974;111(1):81–84. travel. Clin Infect Dis 2002;35(4):446–450. 35. Ghoneim MA, Ashamallah A, El-Bolkainy MN. 15. Poggensee G, Feldmeier H. Female genital schisto- Role of perineuritis in the atonic dilated bilharzial somiasis: facts and hypotheses. Acta Trop 2001;79 ureter. Int Surg 1976;61(8):411–412. (3):193–210. 36. Pawar HN, Abdel-Dayem HM. Diuretic renogra- 16. Martínez S, Restrepo CS, Carrillo JA, et al. Thoracic phy and urodynamic pressure studies in evaluating manifestations of tropical parasitic infections: a pic- dilated bilharzial ureters: a preliminary report. Clin torial review. RadioGraphics 2005;25(1):135–155. Nucl Med 1984;9(7):402–404. 17. Bethlem EP, Schettino G de P, Carvalho CR. 37. Hugosson CO. Striation of the renal pelvis and ure- Pulmonary schistosomiasis. Curr Opin Pulm Med ter in bilharziasis. Clin Radiol 1987;38(4):407–409. 1997;3(5):361–365. 38. el-Badawi AA. Bilharzial polypi of the urinary blad- 18. Cooke GS, Lalvani A, Gleeson FV, Conlon CP. der. Br J Urol 1966;38(1):24–35. Acute pulmonary schistosomiasis in travelers re- 39. Farrell B, Martinez R. Urinary schistosomiasis: lit- turning from Lake Malawi, sub-Saharan Africa. erature review and case presentation. Appl Radiol Clin Infect Dis 1999;29(4):836–839. 1995;24:19. 19. Doherty JF, Moody AH, Wright SG. Katayama fe- 40. Al-Ghorab MM, Rahman MA, El-Rifaie M, et al. ver: an acute manifestation of schistosomiasis. BMJ Radiologic findings of bilharzial (schistosomal) con- 1996;313(7064):1071–1072. tracted bladder. Urology 1978;11(3):303–305. 20. Ross AG, Vickers D, Olds GR, Shah SM, McManus 41. Girges MR. The syndrome of bladder-neck ob- DP. Katayama syndrome. Lancet Infect Dis 2007;7 struction and ureteric fibrosis in Schistosoma hae- (3):218–224. matobium infection. J Trop Med Hyg 1966;69(8): 21. Mosunjac MB, Tadros T, Beach R, Majmudar B. 187–188. Cervical schistosomiasis, human papilloma virus 42. Shokeir AA, Ibrahim AM, Hamid MY, Shalaby MA, (HPV), and human immunodeficiency virus (HIV): Hussein HE, Badr M. Urinary bilharziasis in upper a dangerous coexistence or coincidence? Gynecol Egypt. I. A clinicopathological study. East Afr Med J Oncol 2003;90(1):211–214. 1972;49(4):298–311. 22. Gryseels B, Polman K, Clerinx J, Kestens L. Hu- man schistosomiasis. Lancet 2006;368(9541): 1106–1118. 23. Moudgil A, Kosut J. Urinary schistosomiasis: an uncommon cause of gross hematuria in the indus- trialized countries. Pediatr Nephrol 2007;22(8): 1225–1227. 1046 July-August 2012 radiographics.rsna.org

43. Shokeir AA, Ibrahim AM, Hamid MY, Shalaby MA, 60. Hanafy HM, Youssef TK, Saad SM. Radiologic Hussein HE, Badr M. Urinary bilharziasis in upper aspects of bilharzial (schistosomal) ureter. Urology Egypt. II. A bacteriological study. East Afr Med J 1975;6(1):118–124. 1972;49(4):312–326. 61. Schwartz E, Pick N, Shazberg G, Potasman I. Hem- 44. Pollack HM, Banner MP, Martinez LO, Hodson CJ. atospermia due to schistosome infection in travelers: Diagnostic considerations in urinary bladder wall diagnostic and treatment challenges. Clin Infect Dis calcification. AJR Am J Roentgenol 1981;136(4): 2002;35(11):1420–1424. 791–797. 62. McKenna G, Schousboe M, Paltridge G. Subjective 45. Fataar S, Rudwan M, Bassiony H, Satyanath S. CT change in ejaculate as symptom of infection with of genitourinary calcification due to schistosomiasis. Schistosoma haematobium in travellers. BMJ 1997; Australas Radiol 1990;34(3):234–237. 315(7114):1000–1001. 46. Pulvertaft R, Hurst G. Bladder calcification related 63. Murdoch DR. Hematospermia due to schistosome to end-stage renal failure. Br J Radiol 1984;57(676): infection in travelers. Clin Infect Dis 2003;36(8): 335–336. 1086. 47. Dyer RB, Chen MY, Zagoria RJ. Abnormal calcifi- 64. Ramchandani P, Banner MP, Pollack HM. Imaging cations in the urinary tract. RadioGraphics 1998;18 of the seminal vesicles. Semin Roentgenol 1993;28 (6):1405–1424. (1):83–91. 48. Cheever AW, Young SW, Shehata A. Calcification of 65. Jiménez-Cruz JF, Tormo FB, Gómez JG. Treatment Schistosoma haematobium eggs: relation of radio- of chronic prostatitis: intraprostatic antibiotic injec- logically demonstrable calcification to eggs in tissues tions under echography control. J Urol 1988;139(5): and passage of eggs in urine. Trans R Soc Trop Med 967–970. Hyg 1975;69(4):410–414. 66. Shukla-Dave A, Hricak H, Eberhardt SC, et al. 49. Young RH. Pseudoneoplastic lesions of the urinary Chronic prostatitis: MR imaging and 1H MR spec- bladder and urethra: a selective review with em- troscopic imaging findings—initial observations. phasis on recent information. Semin Diagn Pathol Radiology 2004;231(3):717–724. 1997;14(2):133–146. 67. Maeda H, Toyooka N, Kinukawa T, Hattori R, 50. Thrasher JB, Rajan RR, Perez LM, Humphrey PA, Furukawa T. Magnetic resonance images of hema- Anderson EE. Cystitis glandularis: transition to tospermia. Urology 1993;41(5):499–504. adenocarcinoma of the urinary bladder. N C Med 68. Worischeck JH, Parra RO. Chronic hematospermia: J 1994;55(11):562–564. assessment by transrectal ultrasound. Urology 1994; 51. Capozza N, Collura G, Nappo S, de Dominicis M, 43(4):515–520. Francalanci P, Caione P. Cystitis glandularis in chil- 69. Schnall MD, Pollack HM, Van Arsdalen K, Kressel dren. BJU Int 2005;95(3):411–413. HY. The seminal tract in patients with ejaculatory 52. Murphy WM, Grignon DJ, Perlman EJ. Tumors of dysfunction: MR imaging with an endorectal surface the kidney, bladder, and related urinary structures. coil. AJR Am J Roentgenol 1992;159(2):337–341. Washington, DC: American Registry of Pathology, 70. Popken G, Wetterauer U, Schultze-Seemann W, 2004; 394. Deckart A, Sommerkamp H. Transurethral resection 53. Shokeir AA. Squamous cell carcinoma of the blad- of cystic and non-cystic ejaculatory duct obstruc- der: pathology, diagnosis and treatment. BJU Int tions. Int J Androl 1998;21(4):196–200. 2004;93(2):216–220. 71. Patel PS, Wilbur AC. Cystic seminal vesiculitis: CT 54. Wong-You-Cheong JJ, Woodward PJ, Manning MA, demonstration. J Comput Assist Tomogr 1987;11 Sesterhenn IA. Neoplasms of the urinary bladder: (6):1103–1104. radiologic-pathologic correlation. RadioGraphics 72. Sue DE, Chicola C, Brant-Zawadzki MN, Scidmore 2006;26(2):553–580. GF, Hart JB, Hanna JE. MR imaging in seminal 55. Narumi Y, Sato T, Hori S, et al. Squamous cell carci- vesiculitis. J Comput Assist Tomogr 1989;13(4): noma of the uroepithelium: CT evaluation. Radiology 662–664. 1989;173(3):853–856. 73. Corachan M, Valls ME, Gascon J, Almeda J, Vilana 56. Wong JT, Wasserman NF, Padurean AM. Bladder R. Hematospermia: a new etiology of clinical inter- squamous cell carcinoma. RadioGraphics 2004;24 est. Am J Trop Med Hyg 1994;50(5):580–584. (3):855–860. 74. Mohammed AZ, Edino ST, Samaila AA. Surgical 57. Dondalski M, White EM, Ghahremani GG, Patel pathology of schistosomiasis. J Natl Med Assoc SK. Carcinoma arising in urinary bladder diver- 2007;99(5):570–574. ticula: imaging findings in six patients. AJR Am J 75. Soans B, Abel C. Ultrasound appearance of schisto- Roentgenol 1993;161(4):817–820. somiasis of the testis. Australas Radiol 1999;43(3): 58. Serretta V, Pomara G, Piazza F, Gange E. Pure 385–387. squamous cell carcinoma of the bladder in western 76. Woodward PJ, Schwab CM, Sesterhenn IA. Extra- countries: report on 19 consecutive cases. Eur Urol testicular scrotal masses: radiologic-pathologic cor- 2000;37(1):85–89. relation. RadioGraphics 2003;23(1):215–240. 59. Mostafa MH, Sheweita SA, O’Connor PJ. Relation- 77. Richens J. Genital manifestations of tropical dis- ship between schistosomiasis and bladder cancer. eases. Sex Transm Infect 2004;80(1):12–17. Clin Microbiol Rev 1999;12(1):97–111. 78. Goldsmith PC, Leslie TA, Sams V, Bryceson AD, Allason-Jones E, Dowd PM. Lesions of schistosomiasis mimicking warts on the vulva. BMJ 1993;307 (6903):556–557.

This journal-based CME activity has been approved for AMA PRA Category 1 CreditTM. See www.rsna.org/education/rg_cme.html. Teaching Points July-August Issue 2012

Genitourinary Schistosomiasis: Life Cycle and Radiologic-Pathologic Findings Haytham M. Shebel, MD • Khaled M. Elsayes, MD • Heba M. Abou El Atta, MBBCh, PhD • Yehia M. El - guindy, MBBCh • Tarek A. El-Diasty, MD

RadioGraphics 2012; 32:1031–1046 • Published online 10.1148/rg.324115162 • Content Codes:

Page 1035 The deposition of eggs in the bladder and ureter induces a chronic granulomatous reaction. […] Cystitis resembling that in tuberculosis results in “sandy patches” on the bladder wall that, in severe cases, may become a network of dense concentric calcifications. The degree of calcification is roughly correlated with the number of eggs deposited.

Page 1035 In long-standing infections, a cellular reaction to dead ova produces calcification and fibrosis, which are important contributors to squamous metaplasia and squamous cell carcinoma.

Page 1037 Radiologic imaging manifestations of urinary tract schistosomiasis are observed mainly in the ureters and bladder. The kidneys appear normal until a late stage of disease.

Page 1037 The peristaltic movement of the ureter is affected by two main factors: ureteral stricture due to fibrosis, and mural calcification that begins in the bladder wall. Fibrosis of the ureteral wall and periureteral tissue affects the nerve plexus of the ureter, causing hypotonia mainly in the distal ureteral segment; peristalsis in the proximal ureteral segment (the segment between the ureteropelvic junction and the iliac vessels) is normal until the advanced stage of fibrosis, in which the whole ureter is involved (31,34,35).

Page 1044 The male genitals are more commonly affected by schistosomiasis than the female genitals.