tumors and tumorlike lesions of the testis

Testicular Tumors and Tumor-like Lesions:

Radiologic-Pathologic Correlation

From the Archives of the AFIP. Radiographics. 2002;22:189-216

Testicular Neoplasia Testicular carcinoma most common malignancy- 15–34 year.

Testicular tumors categorized into germ & non–germ cell tumors.

Non-primary tumors as lymphoma, leukemia & metastases can manifest as testicular masses.

Peak prevalence of testicular tumors

25–35 years.

71–90 years- lymphoma & metastasis.

Infants, with rapid decline to nadir for boys 10 years of age.

Survival rates for patients with testicular carcinoma 95%.

Testicular Neoplasia- Presentations

Painless scrotal mass.

Heaviness or fullness in lower abdomen or scrotum.

Pain in 10%- misdiagnosed as orchitis.

Tumors may undergo regression, necrosis & scarring “burned-out germ cell tumors”- normal or small testes at presentation.

Burned-out germ cell tumors & tumors with aggressive histology may present with metastases.

Hormonally active tumors- endocrine abnormalities, commonly gynecomastia.

Embryologic Development

No morphologic sexual differentiation until 7th W- indifferent stage.

Undifferentiated gonad- 3 cell types: mesenchyme, mesothelium & germ cells.

During indifferent stage, genital ridges form on both sides of midline from mesenchyme condensation & are covered by mesothelium-Subsequent proliferation forms primitive sex cords.

Primordial germ cells form in wall of yolk sac, then migrate along hindgut to be incorporated into primitive sex cords.

Embryologic Development Y chromosome- undifferentiated gonad into

testis.

Primitive sex cords form seminiferous tubules from 2 cell lines:

Mesothelium- Sertoli cells.

Migrated germ cells- spermatogonia.

Mesenchyme between seminiferous tubules- Leydig cells.

Tunica albuginea forms.

At 8 weeks, Leydig cells secrete testosterone- mesonephric (wolffian) ducts differentiate into epididymis, vas deferens, seminal vesicles & ejaculatory ducts.

Embryologic Development

Between 7th & 12th weeks, testes contract and become more ovoid as they descend into pelvis.

Until 7th month, near deep inguinal ring, when they begin descent through inguinal canal into twin scrotal sacs.

Anatomy & Histologic Characteristics

Tunica albuginea covered by tunica vaginalis.

Densely packed seminiferous tubules- tubuli recti- rete testis at hilum.

Rete testis converges posteriorly to form 15–20 efferent ductules that penetrate through tunica albuginea “Mediastinum testis” to form head of epididymis.

Efferent ductules converge to form single convoluted tubule- exits epididymis as vas deferens.

Anatomy & Histologic Characteristics

200–300 lobules- each 400–600 seminiferous tubules.

Interstitium: between seminiferous tubules- connective tissue, lymphatics, blood vessels, mast cells & Leydig cells.

Seminiferous tubules- two cell types: Germ cells: spermatogenic germ cells. Sertoli cells: Support for maturing germ cells+ phagocytosis

of degenerating germ cells. Tight junctions- blood-testis barrier. Leydig cells: testosterone production.

T0 = No evidence of Tumor T1s = Intratubular, pre invasive T1 = Confined to Testis T2 = Invades beyond Tunica Albuginea or into

Epididymis T3 = Invades Spermatic Cord T4 = Invades Scrotum

N1 = Single < 2 cm N2 = Multiple < 5 cm / Single 2-5 cm N3 = Any node > 5 cm

Imaging- Ultrasonography 100% sensitive Intra- versus extra-testicular- cystic or solid.

High frequency transducer with adequate penetration- 5–10 MHz.

Homogeneous, medium-level, granular echotexture.

Tunica albuginea not seen separately- echogenic line mediastinum testis.

Epididymis: iso- or slightly hyperechoic to testis.

Imaging- Ultrasonography

Solid testicular masses- malignant.

Most testicular tumors hypoechoic- heterogeneous, with increased echogenicity, calcifications & cysts.

Larger tumors more vascular.

Color Doppler: prepubertal with subtle gray-scale findings.

MRI: problem solving tool when US inconclusive + cryptorchidism.

Imaging- MRI

Surface coil- superior signal-to-noise ratios.

Patient supine- towel under scrotum- penis on abdomen- warm towel draped over scrotum with coil on it.

Suspected cryptorchidism- abdomen & pelvis.

Axial & coronal SE T1- WI.

Axial, coronal & sagittal FSE T2- WI

Superior & inferior saturation bands eliminate ghosting artifacts.

Gadolinium- indeterminate scrotal masses.

For staging, axial T1- WI of abdomen adenopathy.

Imaging- MRI

Homogeneous intermediate signal on T1-WI & high signal “< fluid” on T2-WI.

Tunica albuginea- thin low-signal band.

Internal architecture on T2- WI thin low-signal septa radiating back toward mediastinum testis which forms band along posterior margin of testis.

Epididymis: iso- or slightly hypointense relative to testis on T1- WI & hypointense on T2- WI.

Germ Cell Tumors- Pathogenesis

Intratubular germ cell neoplasia precursor of most germ cell tumors- equivalent of carcinoma in situ- 50% develop invasive tumor in 5 years.

Abnormal cells develop either along:

Unipotential gonadal line- seminoma

Totipotential cell line- non-seminomatous tumors

Largely undifferentiated- embryonal carcinoma.

Extra-embryonic differentiation- yolk sac tumors, choriocarcinoma.

Embryonic differentiation- teratoma.

Mixed germ cell tumor.

Seminomatous & non-seminomatous germ cell tumors.

Germ Cell Tumors- Spread

Lymphatic- hematogenous- direct.

Most germ cell tumors spread via lymphatics except choriocarcinoma.

Lymphatic involvement in step-wise fashion- basis for modern surgery-dissections of retroperitoneal nodes spare sympathetic nerves involved in antegrade ejaculation.

Testicular lymphatic drainage follows testicular veins

Right: interaortocaval chain at L2.

Left: left paraaortic nodes bounded by renal vein, aorta, ureter, IMA.


Crossover of lymphatic involvement in right-to-left fashion.

Left-to-right crossover rare. As tumor volume increases- spread from

first-echelon nodes to common, internal & external iliac nodes.

Tumor within epididymis can spread directly to external iliac nodes.

Skin involvement may directly spread to inguinal nodes- transscrotal orchiectomy contraindicated- inguinal approach.


Hematogenous spread late for any germ cell tumor- primary mode for choriocarcinoma.

Pulmonary metastases most common- liver, brain & bone.

Brain metastases common with choriocarcinoma.

Metastases may have histologic characteristics different from primary tumor- totipotential nature of germ cells.

TNM classification: local tumor extent, lymph node size, distant metastases & serum markers.

Low-stage: tumors confined to testis, epididymis, or spermatic cord (T1–T3) - mild to moderate adenopathy (N1 & N2).

Advanced-stage: tumors invading scrotal wall (T4), significant retroperitoneal adenopathy (N3), or visceral metastases (M1).

Germ Cell Tumors- Tumor Markers

Alpha-fetoprotein: protein produced early in gestation by liver, GIT, & yolk sac- elevated in yolk sac tumors & mixed germ cell tumors with yolk sac elements- rarely teratomas with enteric mucous glands or hepatoid cells.

Human chorionic gonadotropin: glycoprotein produced by syncytiotrophoblasts- level elevated in tumors containing syncytiotrophoblasts “seminomas or choriocarcinomas”.

Elevated in > 80% non-seminomatous germ cell tumors.

Serial serum levels quantify response to treatment & predict recurrence.

Lactate dehydrogenase: produced by multiple organs- < specific.


Unipotential gonadal line- seminoma.

Totipotential cell line- non-seminomatous tumors.



Extra-embryonic differentiation- yolk sac tumors,

choriocarcinoma.


Germ Cell Tumors- Seminoma

35%–50% of all germ cell tumors.

15% have syncytiotrophoblasts.

Seminomas

Average 40 Y.

75% limited to testis.

20% retroperitoneal adenopathy.

5% extranodal metastases.

Small well-defined lesion to large masses replacing testicle.

Histology: resembles primitive germ cells + lymphoid infiltrate.

Germ Cell Tumors- Seminoma- Imaging

Reflect uniform cellular nature.

US: uniformly hypoechoic.

MRI: T2 homogeneous hypointense-

larger tumors heterogeneous.

Lobulated or multinodular- nodules commonly in continuity- rarely true multifocal nodules.

Bilateral tumors in 2% of patients, always asynchronous.

Germ Cell Tumors- Seminoma






choriocarcinoma.



Non- Seminomatous Germ Cell Tumors- Embryonal Carcinoma

Primitive anaplastic epithelial cells resembling early embryonic cells.

Second most common histologic type.

Pure form 2%–3% of testicular tumors- 87% of mixed germ cell tumors.

25–35 years.

Often smaller than seminoma at presentation but more aggressive.

Tunica albuginea may be invaded- tumor borders less distinct, blending into adjacent parenchyma.

US: > heterogeneous & ill-defined than seminomas.

Non- Seminomatous Germ Cell Tumors- Embryonal Carcinoma






choriocarcinoma.



Non- Seminomatous Germ Cell Tumors- Yolk Sac Tumor

Endodermal sinus tumors.

80% of childhood testicular tumors- before 2Y.

Pure form rare in adults- 44% of adult mixed germ cell tumor.

Alpha-fetoprotein elevated in > 90%.

Imaging non-specific, especially in children- testicular enlargement with no defined mass.

Treatment- adults= non-seminomatous tumors.

Treatment- Pediatric: tumor confined to testis + alpha-fetoprotein not elevated- orchiectomy +close monitoring. Relapse, chemotherapy.

Non- Seminomatous Germ Cell Tumors- Choriocarcinoma

Rare- pure form < 1% of patients- 8% of mixed germ cell tumors.

2nd & 3rd decades.

Highly malignant- cyto- & syncytiotrophoblasts.

US: isoechoic +/- invasion of tunica albuginea.

Early widespread metastasis- lung, liver, GIT & brain- Primary & metastases hemorrhagic.

Elevated HCG- gynecomastia in 10%.

Death within 1 year- Mixed germ cell tumors with choriocarcinoma of better prognosis.

Very high HCG-poor prognosis.

Non- Seminomatous Germ Cell Tumors- Choriocarcinoma






choriocarcinoma.



Non- Seminomatous Germ Cell Tumors- Teratoma

2nd after yolk sac tumor in children<4 Y.

Pure form rare in adults- 50% of adult mixed germ cell tumor.

Complex- disorderly arrangement of adult & fetal tissues, with 3 germ layers “endoderm, mesoderm, & ectoderm” involved.

Sub-classified into mature, immature & with malignant areas.

Dermoids, most common teratomatous lesion in ovary- minority of testicular teratomas.

Non- Seminomatous Germ Cell Tumors- Teratoma Complexity reflected in US appearance- complex well-circumscribed

masses; anechoic or complex cysts, cartilage, calcification & fibrosis.

Biologic behavior depending on pubertal status.

Pre-pubertal- pure teratomas benign even histologically immature.

Postpubertal- mature or immature can metastasize- metastases may contain non-teratomatous germ cell elements.

Mature teratoma not equated with benignity.

Non- Seminomatous Germ Cell Tumors- Teratoma

Non- Seminomatous Germ Cell Tumors- Epidermoid Cysts

Monodermal development of teratoma, or squamous metaplasia of surface mesothelium.

1% of testicular tumors.

Keratinizing, stratified, squamous epithelium with defined fibrous wall- benign with no malignant potential.

Although pathologically true cysts- filled with cheesy laminated material that appears solid on imaging.

Non- Seminomatous Germ Cell Tumors- Epidermoid Cysts

Laminated morphology reflected in imaging.

US:

Well-circumscribed, round to oval mass with hyperechoic wall +/- calcified.

May be hypoechoic.

Laminations- onion-skin; ringed appearance.

MRI: "target" appearance, with low-signal capsule. Layers of keratinized material within lesion rich in water & lipid- areas of high signal.

Non- Seminomatous Germ Cell Tumors- Epidermoid Cysts Radiologic appearance characteristic & not pathognomonic-

Teratomas & other malignant tumors.

Irregular border suggest malignancy.

As carcinoma cannot be completely excluded, orchiectomy performed.

If strong likelihood of epidermoid cyst, testis-sparing enucleation.






choriocarcinoma.



Non- Seminomatous Germ Cell Tumors- Mixed Germ Cell Tumor

Contain > one germ cell component.

Of non-seminomatous germ cell tumors, mixed germ cell tumors much > than any pure histologic forms- 32%–60% of all germ cell tumors.

Any combination of cell types- embryonal carcinoma most common component.

Age of presentation 30 Y.

Imaging findings variable, reflecting diversity.

Non-seminomatous tumors not radiosensitive as seminomas- chemotherapy rather than radiation therapy

Non- Seminomatous Germ Cell Tumors- Mixed Germ Cell Tumor

After treatment, CT often show decrease in attenuation & size of retroperitoneal masses- typically interpreted as necrosis-Evolution into more benign histologic type.

Resected treated masses- 40% necrosis or fibrosis- 40% mature teratoma- 20% areas of residual tumor.

Mass containing only mature teratoma should be resected- mature teratoma can grow despite benign histology “growing teratoma syndrome”, or transform to more aggressive type.

Non- Seminomatous Germ Cell Tumors- Regressed Germ Cell Tumors

= "burned-out" germ cell tumor.

Metastases though primary involuted.

Pathogenesis: high metabolic rate of tumor causes it to rapidly outgrow its blood supply.

Clinically occult- testis normal to small.

US: search for primary regressed tumor- variable appearance; small, can be hypo-, hyperechoic or focal calcification.

Histology: minute amounts of residual tumor or dense deposits of collagen.

Seminoma Embryonal Carcinoma

Yolk sac tumor Choriocarcinoma Teratoma

Epidermoid cyst Regressed germ cell tumor

Germ Cell Tumors- DDx- Primary Extragonadal Germ Cell Tumors

Retroperitoneum, mediastinum, sacrococcygeal area & pineal gland- differentiate from regressed germ cell tumor with metastasis.

Pathogenesis:

Aberrant migration of germ cells from yolk sac.

Persistent pluripotential cells in primitive rests during somatic development.

In retroperitoneal germ cell tumor, consider metastatic disease as retroperitoneal germ cell tumors are likely of testicular origin rather than primary- Testes thoroughly evaluated.

Testicular Carcinoma- Risk Factors

Prior testicular tumor: risk of contralateral tumor > 20 times.

Positive family history: Testicular carcinoma in first-degree relative increases risk factor six times.

Infertility:

Cryptorchidism & gonadal dysgenesis implicated in both.

Biopsies of subfertile men- intratubular germ cell neoplasia.

Patients with testicular carcinoma- higher serum antisperm antibodies & 25% have defective spermatogenesis.

Intersex syndromes: gonadal dysgenesis, true hermaphroditism & pseudohermaphroditism.

Cryptorchidism

Testicular Carcinoma- Risk Factors- Cryptorchidism

Incomplete descent of testicles to scrotum- 6% term infants- majority distal to external inguinal ring & palpable- descend into scrotum by 1 year.

Non-palpable testicles usually within inguinal canal- anywhere along path of descent- 15%–63% agenetic.

MRI: localizing non-palpable undescended testes + differentiating from agenesis.

Gadolinium-enhanced venography: agenesis from ectopia.

Testicular Carcinoma- Risk Factors- Cryptorchidism

Cryptorchidism in 3.5%–14.5% of patients with testicular carcinoma.

Pathogenesis: cryptorchidism manifestation of generalized embryogenesis defect that results in bilateral dysgenetic gonads.

Risk for testicular carcinoma in contralateral testis, even normally descended

Orchiopexy does not decrease risk of tumor.

Risk of carcinoma increases with degree of ectopy.

Seminomas, especially abdominally.

Testicular Microlithiasis

Relatively uncommon- 0.6% of patients.

Historically, innocuous incidental finding.

Associations: cryptorchidism, infertility, Klinefelter syndrome, Down syndrome, atrophy, alveolar microlithiasis, and, most important, testicular carcinoma.

Sertoli cells: phagocytosis of degenerated intratubular debris- defective activity.

Histopathology- laminated concretions within lumen of seminiferous tubules.

Prevalence of carcinoma- 40%.


Microcalcifications result from abnormal testis- microcalcifications incite damage.

Rule out mass.

Compelling questions:

What is risk of developing cancer?

How closely should patients be followed?

Cast JE. Testicular microlithiasis: prevalence and tumor risk in a population referred for scrotal sonography. AJR; 175:1703-6.

Ganem JP. Testicular microlithiasis is associated with testicular pathology. Urology; 53:209-13.

Furness PD. Multi-institutional study of testicular microlithiasis in childhood: a benign or premalignant condition?. J Urol; 160:1151-4.

Gooding GA. Detection of testicular microlithiasis by sonography. AJR; 168:281-2.

Non–Germ Cell Tumors- Sex Cord, Stromal & Sex Cord–Stromal–Germ Cell Tumors

Leydig cell tumors.

Sertoli cell tumors.

Granulose cell tumors.

Fibroma- thecomas.

Sex cord– stromal tumors.

Sex cord– stromal– germ Cell tumors.

Non–Germ Cell Tumors- Sex Cord, Stromal & Sex Cord–Stromal–Germ Cell Tumors

4% of testicular tumors from cells forming sex cords “Sertoli cells” & interstitial stroma “Leydig cells”.

Higher in pediatric- 10%–30% of testicular neoplasms.

90% of non–germ cell tumors benign.

No radiologic criteria differentiating benign from malignant.

Even histologically, difficult to determine biologic behavior.

Tumors without aggressive histology may metastasize.

Non–Germ Cell Tumors- Leydig Cell Tumors 1%–3% of testicular tumors.

Any age group.

30% have endocrinopathy secondary to androgens or estrogens- precocious virilization, gynecomastia, or decreased libido.

Small solid masses- may show cystic areas, haemorrhage, or necrosis.

Sonographic appearance variable & indistinguishable from germ cell tumors.

Non–Germ Cell Tumors- Sertoli Cell Tumors

< 1% of testicular tumors.

Less likely hormonally active.

Typically well-circumscribed, unilateral, round to lobulated masses.

Large-cell calcifying Sertoli cell tumor:

Pediatric age group.

Multiple & bilateral masses- large areas of calcification.

Association: Peutz-Jeghers & Carney syndromes.

Sertoli Cell Tumors


Epiderrmoid cyst

Regressed Germ Cell Tumor

http://radiographics.rsnajnls.org/cgi/content/full/22/1/189/F17A

Non–Germ Cell Tumors-Gonadoblastoma

Category containing both sex cord–stromal elements & germ cells.

Occur with gonadal dysgenesis & intersex syndromes.

80% phenotypically female.

Lymphoma Primary- manifestation of occult disease- site of recurrence.

5% of testicular tumors- < 1% of lymphoma patients.

Most common bilateral testicular tumor- synchronous or metachronous.

Epididymis & spermatic cord involved.

B-cell lymphomas- diffuse large cell.

Discrete hypoechoic lesions- may completely infiltrate testicle.

Leukaemia

Primary leukemia of testis- rare.

Testis common site of leukemia recurrence in children, with 80% in bone marrow remission.

Blood-testis barrier allows leukemic cells to be "hidden" during chemotherapy.

Clinical characteristics & sonographic appearance quite varied, as tumors may be unilateral or bilateral, diffuse or focal, hypo- or hyperechoic.

Metastases

Other than from lymphoma & leukaemia- rare.

Prostate & lung cancer.

Generally with widespread disease & rarely presenting complaint.

Tumor-like Lesions

Orchitis- hemorrhage- ischemia or infarction. Ill defined than tumors, with overlap in US appearances.

Clinical presentation key- acute scrotum.

Be cautious, since tumors can manifest with pain- dull ache.

US findings of hemorrhage & orchitis evolve rapidly.

Granulomatous orchitis More indolent course- can manifest as testicular mass

TB, syphilis, fungi & parasites- granulomatous epididymo-orchitis.

Epididymis first > testis.

Isolated testicular mass extremely unusual.

Tumor-like Lesions- Tubular Ectasia of Rete Testis

Normal variant- mistaken for neoplasm.

2ry to obstruction in epididymis or efferent ductules.

Posteriorly by mediastinum- composed of series of dilated tubules.

US: resemble hypoechoic mass in cross section- careful scanning shows series of dilated tubules- often bilateral- frequently spermatocele.

MRI: hypointense on T1- WI & iso- to hyperintense on T2- WI.

Diagnosis prevent orchiectomy.

Tumor-like Lesions- Testicular Cysts

8%–10% of patients.

Tunica albuginea or parenchyma.

Cause of tunica albuginea cysts:

Fluid within small mesothelial rests.

Fluid in blind-ending efferent ductules.

Tunica albuginea cysts peripherally located & may be single or multiple.

Classic location & appearance makes diagnosis straightforward.

Tumor-like Lesions- Testicular Cysts

Intratesticular cysts problematic- DDx cystic neoplasms, typically teratomas.

Cystic lesion with solid components- consider malignant.

Benign cysts incidental & not palpable.

Usually near mediastinum testis- originate from rete testis.

Dilated rete testis- not uncommon.

Tumor-like Lesions- Adrenal Rests

Rare- with congenital adrenal hyperplasia & rarely Cushing syndrome.

Aberrant adrenal rests trapped in developing gonad.

Usually < 5 mm- testis & surrounding tissues in 7.5%–15% of newborns & 1.6% of adults.

Typically multiple, bilateral & eccentric.

Elevated levels of ACTH- masses.

Treatment: glucocorticoids- stabilization or regression of masses.

Tumor-like Lesions- Adrenal Rests

US: variable- predominantly hypoechoic masses- heterogeneously hyperechoic with shadowing.

MRI: low signal on T1- & T2- WI.

If there is question about diagnosis testicular vein sampling show elevated cortisol levels compared with peripheral blood levels.

Tumor-like Lesions- Sarcoidosis

Chronic granulomatous disease- 5% genital involvement.

Testicular sarcoidosis more common in African-Americans.

Epididymis > testis.

Testicular lesions can be solitary- typically multiple, small, bilateral masses.

Fournier Gangrene

=necrotizing fasciitis- rapidly progressive fasciitis of perineum- described in 1883 by Jean Alfred Fournier, a French venereologist*.

Most cases occur in diabetic men 50–70 years old- described in women.

Often there is point of entry (i.e., urethral, rectal, or subcutaneous tissue) by polymicroorganisms- rate of fascial necrosis 2–3 cm/h.

Most commonly isolated organisms: Klebsiella, Proteus, Streptococcus, Staphylococcus, Peptostreptococcus, and Escherichia coli- soft-tissue gas comes from by-products of anaerobic metabolism.

Sudden perineal & and swelling + fever & leukocytosis- examination reveals pain, redness & swelling of perineal area- sometimes crepitus.

Treatment: immediate radical débridement of all necrotic areas.

Fournier JA. Gangrène foudroyante de la verge. Semaine Medecine 1883; 3:345-348.

Fournier Gangrene

Radiography: soft-tissue edema of perineal tissues- subcutaneous emphysema may be seen tracking along extent of involved tissue planes.

US: thickened scrotal skin- gas within scrotal skin, seen as hyperechoic foci with dirty shadowing “ pathognomonic”- hyperechoic foci not within testicle and should not be confused with calcifications of testicular microlithiasis, germ cell tumors, teratomas, teratocarcinomas, sarcoidosis, tuberculosis, or chronic infarct- testicle often normal because of separate blood supply.

CT: fascial thickening and fat stranding of involved areas- CT can more completely depict extent of soft-tissue gas and can often show cause of Fournier gangrene, such as perianal abscesses, incarcerated inguinal hernias, or fistulous tracts.

Fournier Gangrene

Differential diagnosis for acute scrotal pain: testicular trauma, testicular torsion, acute epididymo-orchitis, and Fournier gangrene.

Testicular trauma (blunt or penetrating) distinguished from Fournier gangrene based on history and physical evidence of trauma.

Although testicular torsion and acute epididymo-orchitis can manifest with acute scrotal pain without history of trauma and examination can show swollen, erythematous scrotum, color Doppler flow US can help distinguish between these diagnoses

Testicular torsion: Color Doppler US 86% sensitive in showing absent testicular and epididymal flow.

Acute epididymo-orchitis: increased epididymal and/or testicular flow.

Fournier Gangrene

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tumors and tumorlike lesions of the testis

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