Clinicopathological Study of Regressed Testicular Tumors

(Apparent Extragonadal Germ Cell Neoplasms)

Javier C. Angulo,* Javier González, Nuria Rodríguez, Emilio Hernández,Carlos Núñez, Jose M. Rodríguez-Barbero, Alicia Santana and José I. LópezFrom the Departments of Urology and Pathology, Hospital Universitario de Getafe, Servicio Madrileño de Salud (JCA, JG, EH, CN, JMRB),Universidad Europea de Madrid (JCA, JG, EH, CN, JMRB) and Department of Pathology, Hospital Universitario Príncipe de Asturias (AS),Madrid, Department of Urology, Hospital General Yagüe (NR), Burgos, and Department of Pathology, Hospital Universitario de Cruces,Euskal Herriko Unibertsitatea/Universidad del País Vasco (JIL), Bizkaia, Spain

Purpose: Testicular germ cell tumors sometimes regress spontaneously andmanifest exclusively by metastasis. We report our experience with extragonadalgerm cell tumors of probable testicular origin to study the frequency of this entity,and clinical, ultrasound and histopathological correlations in a series of patients.Materials and Methods: A retrospective 16-year review of 1.2 million inhabit-ants in Spain revealed 17 with regressed testicular tumors treated at a total of 4institutions. We analyzed clinical information, ultrasound features and his-topathological characteristics of testicular lesions and metastasis, and highlightthe main findings.Results: A primary testicular origin was confirmed in all cases. This entity ismore common than initially suspected since it accounts for 4% of consecutivegerm cell tumors. Clinical manifestations varied according to metastatic site withan abdominal palpable mass (47% of cases), loin pain (35%) and transient testic-ular pain (29%) the most common complaints. No evidence of testicular neo-plasms was found on physical examination in any case. Metastasis histology wasnonseminomatous in 53% of cases, pure seminoma in 29% and mixed in 18%. Themost common ultrasound features were calcifications in 65% of cases, hyperecho-genic linear images in 59% and hypoechogenic nodular areas in 41%. Histologicalfindings consisted of fibrotic areas in 100% of cases, hemosiderin deposits in 65%,seminiferous tubule atrophy in 59% and psammoma bodies in 29%. In testicularparenchyma or spermatic chord intratubular neoplasms and viable tumor fociwere also noted (47% and 41% of cases, respectively).Conclusions: Spontaneous regression of a germ cell testicular tumor should beconsidered in each patient with extragonadal germ cell neoplasms. Ultrasounddiagnosis of and surgical treatment for these primary testicular tumors appearcritical to prevent relapse because residual disease develops in a significantproportion of cases.

Key Words: testis; testicular neoplasms; neoplasms, germ cell and

Abbreviations

and Acronyms

�HCG � � human chorionicgonadotropin

AFP � � fetoprotein

FNAC � fine needle aspirationcytology

RPLND � retroperitoneal lymphnode dissection

Submitted for publication March 22, 2009.* Correspondence: Department of Urology,

Hospital Universitario de Getafe, Carretera deToledo Km 12.500, Getafe 28905, Madrid, Spain(e-mail: jangulo@futurnet.es).

embryonal; neoplasm regression, spontaneous; ultrasonography

EXTRAGONADAL germ cell tumors areuncommon, accounting for only 3% to5% of all germ cell tumors, and ap-proximately 1,000 cases have been de-

scribed to date.1 Since the incidence of

0022-5347/09/1825-2303/0THE JOURNAL OF UROLOGY®

Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION

testicular cancer in Spain is approxi-mately 2 new cases per 100,000 in-habitants per year,2 the estimated in-cidence of extragonadal germ cell

tumors should be 0.06 to 0.1/100,000

Vol. 182, 2303-2310, November 2009Printed in U.S.A.

DOI:10.1016/j.juro.2009.07.045www.jurology.com 2303

REGRESSED TESTICULAR TUMORS2304

inhabitant per year. Two hypotheses were proposedto explain the origin of these tumors, that is theyoriginate from embryonic endodermal cells thatlater fail to migrate toward the gonad or representmetastasis of a primary occult germ cell testiculartumor.3 In accordance with the latter theory a num-ber of typical ultrasound and histological findingsare present in the testis in these patients.4

Extragonadal germ cell neoplasms may be locatedin the mediastinum, retroperitoneum, sacrococcy-geal region and pineal gland, and the most commonhistological entity is pure seminoma.1 There is ageneral belief that mediastinal tumors and lesionslocalized in the central nervous system are almostalways primary and retroperitoneal tumors are met-astatic from a primary testicular focus.4,5 The pri-mary lesion may be occult or clinically unapparentdue to a combination of small size and central tes-ticular location or it may be a true burned out lesionthat has undergone histological changes consistentwith tumor regression or even extinction.

Despite the controversy on the origin of thesetumors it is now assumed that an intratesticularpalpable or impalpable mass in a patient with aretroperitoneal germ cell neoplasm represents theprimary tumor, for which radical orchiectomy is in-dicated. We present clinical, ultrasound and his-topathological correlations in 17 patients with ex-tragonadal germ cell neoplasms and apparentlynormal testes on physical examination due to pri-mary tumor regression. Epidemiological, therapeu-tic and prognostic implications associated with thisdistinct presentation are discussed.

PATIENTS AND METHODS

Databases of germ cell tumors from 4 Spanish hospitalscovering an overall 1,200,000 inhabitant population wereretrospectively analyzed. After reviewing records on 421germ cell tumors from 1993 to 2008 we found 17 cases(4.04%) of extragonadal germ cell neoplasms with ap-parently normal testes in which clinical and ultrasoundfeatures led to suspicion of regressed primary testicularcancer. They were all of the patients with presumedextragonadal tumors who presented to the institutionsduring the study period. No case of primary mediastinalgerm cell neoplasms was recorded in the series. Histolog-ical diagnosis was confirmed in each case, allowing clini-copathological correlation. Radical orchiectomy was donein all patients except 1 with a solitary testis in whom widebiopsy (partial orchiectomy) was performed. In 14 casesorchiectomy was done after diagnosing extragonadal germcell neoplasms by retroperitoneal mass biopsy or FNACand tumor marker investigation. In 3 cases orchiectomywas initially performed for a vanishing mass (1) or due totransitory testicular enlargement (2). All except 2 patientswith pure seminoma received cisplatinum based systemic

chemotherapy (see table).

Mean patient age was 31 years (range 18 to 46). Allpatients underwent urological assessment, testicular ul-trasound using a 7.5 Hz transducer and thoraco-abdomi-nal computerized tomography. The latter revealed retro-peritoneal lymph nodes in 17 cases, of which 5 hadadditional metastatic foci in lung (2), lung and liver (1),supraclavicular lymph nodes (1) and inguinal nodes (1).RPLND was done in 10 cases. In 5 cases it was doneprimarily, including 3 in which orchiectomy was initiallyperformed, 1 mistaken for renal cancer since the retroper-itoneal mass infiltrated the kidney and 1 mistaken forhepatocarcinoma. RPLDN was done after chemotherapyin another 5 cases. Histopathological diagnoses weremade according to the WHO classification of germ celltesticular tumors.6

AFP and �HCG tumor markers were always investi-gated at diagnosis and at orchiectomy but in 5 patients theretroperitoneal mass had already been excised. In 2 casesthese data were not available and so proper tumor markerinformation was lacking. Three patients with pure semi-noma received radiotherapy. All except 2 patients (88%)with pure seminoma were treated with cisplatinum basedmultidrug chemotherapy. Salvage second line regimenswere used in 2 patients who died with histological evi-dence of choriocarcinoma and incomplete surgical resec-tion (see table). The testis was always removed beforechemotherapy. One of us performed a central pathologyreview (JIL).

RESULTS

Clinical Findings

The table lists clinical presentation in the 17 cases.Clinical presentations were an abdominal palpablemass in 47% of patients, lumbar pain in 35%, asthe-nia in 29%, transient testicular pain in 24%, fatiguein 12%, constipation in 12% and hematuria in 6%.Other local complaints except testicular pain were atransient increase in testicular size in 35% of casesand a vanishing testicular mass in 24%. Of the cases41% showed no local symptoms. No tumor was felton palpation. Testes were atrophic in 35% of pa-tients and normal in 59%, and hydrocele did notallow appropriate examination in 6%. Eight lesions(47%) were on the right side and 9 (53%) were on theleft side, showing no site dominance.

Sometimes diagnosis had been deferred so 29% ofcases presented with massive metastases outsidethe retroperitoneum. Pulmonary metastases weredetected in 3 patients, including 1 with hepatic dis-ease at diagnosis (fig. 1, A). Inguinal and supracla-vicular nodes were present in 1 case each. Of thesepatients, in whom an extremely poor prognosis wasanticipated because of the high metastatic load, only1 remained disease-free at reasonable followup.Massive retroperitoneal involvement was also presentin another 3 cases (18%), including 1 in which ret-roperitoneal disease was interpreted as an atypical

renal mass and left radical nephrectomy was per-

Clinicopathological data on primary germ cell testicular tumor regression

Pt No.—Age Location Presentation Local SymptomsHistology ofMetastases Markers Management Orchiectomy Side Viable Tumor

IntratubularNeoplasm Status (mos followup)

1—18 Retroperitoneal Testicular pain �abdominal mass

Transitoryenlargement

Embryonal Ca �HCG, AFP RPLND � chemotherapy Yes Rt No No No disease evidence (148)

2—20 Retroperitoneal Loin pain � abdominalmass

Transitoryenlargement

Chorioca �HCG Biopsy, chemotherapy �salvage chemotherapy

Yes Rt No No Dead of disease (7)

3—22 Retroperitoneal Renal mass, colic,hematuria � asthenia

Transitoryenlargement

Yolk sac tumor AFP Nephrectomy � RPLND,chemotherapy

Yes Lt Yolk sac tumor Yes No disease evidence (84)

4—24 Retroperitoneal �pulmonary

Fatigue � abdominalmass

None Embryonal Ca �HCG, AFP FNAC, chemotherapy �salvage RPLND

Yes Lt No Yes Dead of disease (30)

5—26 Retroperitoneal �pulmonary

Fatigue None Seminoma �embryonal Ca

�HCG Chemotherapy �salvage RPLND

Yes Rt Seminoma �embryonal Ca

Yes No disease evidence (51)

6—27 Retroperitoneal Constipation �abdominal mass

None Embryonal Ca �HCG Biopsy, chemotherapy �salvage RPLND

Yes Lt No No Unknown

7—39 Retroperitoneal �supraclavicularnodes

Neck mass � asthenia Vanishing mass Teratoca �immature teratoma

�HCG, AFP Biopsy � chemotherapy Yes Rt No No Dead of disease (9)

8—32 Retroperitoneal �inguinal nodes

Loin pain � asthenia Vanishing mass Chorioca �seminoma

�HCG FNAC, chemotherapy �salvage chemotherapy

Yes Lt No No Dead of disease (28)

9—25 Retroperitoneal Loin pain �constipation

None(solitary testis)

Teratoca �HCG Biopsy � chemotherapy Partial Lt No Yes No disease evidence (46)

10—41 Retroperitoneal Abdominal mass None Seminoma �teratoca

�HCG, AFP Biopsy, chemotherapy �salvage RPLND

Yes Lt Seminoma No Disease (18)

11—28 Retroperitoneal Testicular pain Vanishing mass Embryonal Ca Not available RPLND � chemotherapy Yes Rt Embryonal Ca Yes No disease evidence (22)12—19 Retroperitoneal,

lung � liverAbdominal mass �asthenia

Vanishing mass Chorioca �HCG, AFP Biopsy � RPLND,chemoradiotherapy

Yes Rt No No Disease (9)

13—31 Retroperitoneal Testicular pain Transitoryenlargement

Seminoma None Excision � radiotherapy Yes Rt No No No disease evidence (76)

14—35 Retroperitoneal Testicular pain Transitoryenlargement

Seminoma None Biopsy, radiotherapy �chemotherapy

Yes Lt Seminoma Yes No disease evidence (98)

15—46 Retroperitoneal Loin pain None Seminoma None Biopsy, chemotherapy �salvage RPLND

Yes Lt No No No disease evidence (124)

16—38 Retroperitoneal Loin pain � asthenia Transitoryenlargement

Seminoma Not available RPLND � chemotherapy Yes Rt Seminoma Yes No disease evidence (36)

17—44 Retroperitoneal Palpable mass None Seminoma None Excision � radiotherapy Yes Lt Seminoma Yes No disease evidence (29)

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REGRESSED TESTICULAR TUMORS2306

formed. Histological analysis revealed a pure yolksac tumor with positive margins. This patient re-ceived systemic chemotherapy and had no diseaseevidence at 84 months of followup (fig. 1, B). Theremaining 2 cases presented as a pure choriocarci-noma. Surgical resection was impossible in 1 pa-tient, who died after failed salvage chemotherapy 7months after diagnosis (fig. 1, C).7 The remainingpatient with choriocarcinoma underwent segmentalliver resection, lymphadenectomy and radiation,and currently receives chemotherapy (fig. 2, A).

A high degree of suspicion was needed in manycases to assess tumor markers, which were positiveat a different level in all cases of nonseminomatousor mixed histology and negative in all pure semi-noma cases. Overall HCG was increased in 10 cases(59%), AFT was increased in 8 (47%) and neitherwas increased in 5 (29%). Tumor markers were eval-uated before retroperitoneal mass biopsy in only 4

Figure 1. Regressed testicular tumor metastatic presentations.A, pulmonary dissemination. B, retroperitoneal disease mimick-ing giant renal mass. C, massive retroperitoneal disease.

Figure 2. A, pure choriocarcinoma metastatic to liver with cen

scopic view shows irregular scar with seminiferous tubule atrophy, lym

cases (24%), of which 3 showed transitory testicularsymptoms.

Regarding prognosis, 4 of the 17 patients died ofcancer related causes 7, 9, 28 and 30 months afterdiagnosis, and 2 had residual disease at 9 and 18months of followup, respectively. Another 10 pa-tients were disease-free at a mean followup of 71.4months (range 22 to 148). Five and 10 year disease-free survival was achieved by 29.4% and 11.8% ofpatients, respectively. Only 1 patient was lost tofollowup. All patients without disease evidence at 36months of followup or beyond were in the good prog-nosis International Germ Cell Consensus Classifica-tion group. However, 3 of the 4 patients who died ofdisease and 1 of the 2 who had disease at the time ofthis report had poor prognosis lesions according tothis classification.8

Ultrasound Findings

Regarding testicular ultrasound features, disorgani-zation of the sound homogeneous pattern was a con-stant finding suggesting a diagnosis of regressedtesticular neoplasms in all cases, which was con-firmed by orchiectomy. The most common featureswere testicular calcifications, hyperechogenic linearimages and focal or diffuse hypoechogenic lesions.Findings were always unilateral and consistent withthe side of metastasis.

Multiple calcifications present in 11 cases (65%)were usually sparse and 1 to 2 mm but sometimesconfluent, forming highly echogenic foci with a pos-terior acoustic shadow in 2 cases (12%) (fig. 3). Alinear intratesticular focus of high amplitude echowas observed in 9 cases (53%), which was 2 to 28 mm(mean 10.75). This area of increased echogenicitywith faint posterior acoustic shadowing was presentin 7 of 9 cases of pure nonseminomatous histology inthe metastases. A subalbugineal location was themost common site and it tended to transverse the

morrhagic necrosis. Reduced from �100. B, low power micro-

tral he phoplasmatic infiltrate and arcuate vessels. Reduced from �40.

REGRESSED TESTICULAR TUMORS 2307

testis longitudinally. Often the linear focus was sur-rounded by a hypoechoic zone that corresponded tothe fibrous scar produced by tumor regression (fig. 4).Sometimes a hypoechoic zone was the only ultra-sound finding. Some degree of hypoechogenicitypresent in 7 cases (41%) was associated with persis-tent viable testicular tumor (partial tumor regres-sion) in 6. All 5 cases of diffuse hypoechoic lesionsshowed some degree of tumor viability in the form ofpersistent seminoma. Other less common ultra-sound findings were associated with the major pat-terns described, including patched echogenicity in 4cases (24%), significant testicular atrophy in 3 (18%)and some degree of hydrocele in 2 (12%).

Histopathological Findings

Histological types found at metastasis were pureseminoma in 5 cases (29%), mixed tumor with sem-inoma in 3 (18%), mixed tumor without seminoma in

Figure 3. Ultrasound findings in testis of patients with apparentextragonadal neoplasms. A, multiple confluent calcificationsforming highly echogenic foci with posterior acoustic shadow.B, diffuse hypoechoic zone with 1 calcification.

Figure 4. Macroscopic-ultrasound correlation. A, lineal subalbu

B, cut surface of well demarcated, nonpalpable nodular fibrous scar.

1 (6%), pure embryonal carcinoma in 4 (24%), purechoriocarcinoma in 2 (12%), pure teratocarcinoma in1 (6%) and pure yolk sac tumor in 1 (6%) (see table).Typical histopathological testicular findings of re-gressed germ cell neoplasms were multiple. Fibrousscarring with dense, relatively acellular collagenmatrix was present in all orchiectomy specimenswith a variable degree of lymphoplasmacytic infil-trate in 15 cases (88%), hemosiderin deposits inassociation with scarring in 11 (65%), severe semi-niferous tubule atrophy forming ghost tubules in 10(59%) as well as angiomatous foci in 7 (41%) (figs. 2,B and 5, A and B). Coarse intratubular calcificationswere observed in 8 cases (47%), including 4 (24%)with psammoma bodies (fine onionskin-shaped cal-cifications also noted in cryptorchid atrophic testesand testicular microlithiasis with a diffuse pattern).

Tumor regression was complete in 10 cases (59%)but in 7 (41%) residual viable tumor, which was focal(2) or extensive (5), was undergoing the retrogressivescarring process (fig. 5, A and B). The table lists thehistological subtypes of residual and metastatic neo-plasms. Seminoma was the most common persistentneoplasm (5 of 7 cases or 71%), followed by embryonalcarcinoma (2 of 7 or 29%) and yolk sac tumor (1 of 7 or14%). Neoplastic foci were arranged in disperse nestsin dense collagenic stroma at the testicular periphery,even invading the rete testis and the spermatic chord.

Intratubular neoplasms were seen in 8 cases (50%)in adjacent parenchyma, often with coarse intratubu-lar calcifications. Immunostaining for placental alka-line phosphatase contributed to its identification (fig.5, C and D). Prominent Leydig cell clusters were asso-ciated with atrophic changes in the parenchyma pe-ripheral to the scar in 7 cases (41%).

DISCUSSION

A burned out testicular tumor is defined as sponta-neous regression of a testicular germ cell tumor,which after metastatic spread manifests at its pri-

focus of high amplitude echo surrounded by hypoechoic area.

gineal

REGRESSED TESTICULAR TUMORS2308

mary location as a scarring lesion with characteris-tic histological alterations. This type of tumor wasfirst reported in 1927 by Prym in a patient withextragonadal choriocarcinoma, in whom specific his-tological features were found in the orchiectomyspecimen.9 As early as 1961, Azzopardi and Hoff-brand defined the concept of burned out testicularcancer in 17 patients with extragonadal germ celltumors in whom testicular scars were detected withdeposits of different materials, classically named he-matoxiphilic bodies.10

Our experience supports the fact that a primaryextragonadal germ cell tumor should always be con-sidered a burned out testicular neoplasm untilproven otherwise.5,11 Abnormal testicular ultrasoundmakes necessary surgical removal of the involvedtestes since the diagnosis will be uniformly con-firmed and neoplastic persistence will be noted in ahigh proportion of cases.

Several groups have reported burned out tumorultrasound findings.4,11,12 We confirm that hypere-choic zones with high amplitude echoes usually reflecta scarring process with tumor hemorrhagic necrosisand microcalcifications. However, hypoechogenic le-sions represent tumors with a high risk of seminoma-tous persistence. Histological findings in orchiectomyspecimens in our study did not differ from those inprevious reports.10–13 They revealed a high degree ofpersistent intratubular neoplasms and viable tumorfoci in testicular specimens. At least 1 of these entitieswas present in 53% of cases.

Thus, regression of a primary germ cell testiculartumor may be total or partial. A relatively well de-lineated scar and peripheral testicular atrophy withevidence of intratubular neoplasms and/or calcifica-

Figure 5. A, burned out testicular cancer complete regression wifrom �250. B, burned out testicular cancer partial regression withcollagenic stroma. Reduced from �250. C, intratubular germ cLeydig cell clusters. Reduced from �400. D, placental alkalinetumors. Reduced from �400.

tions are the most common findings in cases of com-

plete regression. These neoplasms are classicallytermed burned out cancers. This scarring processmust be distinguished from post-inflammatory scarswith multifocal pattern associated with vascular le-sions (thrombi or vasculitis) and devoid of intratu-bular calcification or neoplasms.13

We also support the notion that testicular tu-mor regression is most commonly associated withseminoma,13–15 although previous reports overrepresent choriocarcinoma based on the low rela-tive frequency of this testicular neoplasm in thegeneral population.16,17 In our series seminomawas most commonly observed in viable testicularneoplastic foci, followed by embryonal carcinomaand yolk sac tumor. However, it is impossible topredict the subtype of regressed germ cell tumorfrom remnant features in the testis in cases ofcomplete regression. Focal intertubular growth isa common finding in seminoma cases. Some ofthem show only intertubular growth and may notproduce a palpable mass and, thus, the neoplasmscan be easily heralded by metastases or foundduring investigation for infertility.14,18 Seminomawith exclusive intertubular growth is character-ized by disperse tumor cells growing between atro-phic tubules associated with lymphocyte infiltrateand mixed with Leydig cell nodules. Since it isclinically and pathologically inconspicuous, it mayalso be discovered by its metastases and be mis-diagnosed as inflammatory atrophy or even par-tially regressed germ cell neoplasms. Althoughtumor was not confirmed in any case in this series,ghost tubules present in 59% of cases were mostlikely secondary to intertubular tumor regres-sion.18 All embryonal carcinoma cases showed in-

ine fibrosis, ghost tubules and scattered siderophages. Reducedstent seminoma growing in disperse nests surrounded by denseor with coarse calcifications, tubular sclerosis and prominent

phatase immunohistochemistry reveals intratubular germ cell

th hyalpersi

ell tumphos

tratubular calcifications that may correspond to

REGRESSED TESTICULAR TUMORS 2309

intratubular embryonal carcinoma regression,13

persisting as viable embryonal carcinoma in thetestis in 40% with this histological pattern in me-tastases.

In a classic autopsy study about 10% of patientswho died of metastatic testicular tumor had re-gressed testicular neoplasms.19 In our experienceat least 25% of the patients died of cancer anddespite aggressive combined therapy there werefew disease-free survivors in the long term, includ-ing 29.4% at 5 and 11.8% at 10 years. Patientswith complete regression did not have a betterprognosis than those with partial regression. Onthe contrary, all patients who were identified tohave died of disease had complete testicular re-gression. However, there was a more favorableprognosis in patients with pure seminoma metas-tases regardless of whether the tumor had re-gressed completely or partially.

For rational management of testicular regressedtumors orchiectomy may not be mandatory.20,21 How-ever, most groups favor radical orchiectomy whenthere are ultrasound changes, testicular atrophy or ahistory of cryptorchidism. Benefit could be achieved byeradicating the primary focus and preventing poten-tial relapse after chemotherapy. Metastatic germ celltumors treated with systemic chemotherapy carry anapproximately 50% risk of persistent tumor cells in thetestis, as shown in reports of delayed orchiectomy afterchemotherapy.12,22–26 Probably in cases of completetumor regression leaving the testis in place maynot negatively impact prognosis. However, we be-lieve that the prognosis of testicular neoplasmregression is serious enough to justify orchiectomyafter suspicious ultrasound in each case. Orchiec-

tomy enables the correct diagnosis and treats neo-

REFERENCES

Alfonso J et al: Tumor testicular fundido scheinlich chorionepithelio

plastic persistence in a significant proportion ofcases. Orchiectomy was always consistent withretroperitoneal metastasis laterality and drivenby testicular ultrasound findings suggesting re-gressed tumor. Cases in a solitary testis or rarecases of bilateral regressed tumors can also bemanaged conservatively by surgery.27

Clinical presentation varies in cases of apparentextragonadal germ cell neoplasms due to testiculartumor regression and is often revealed by a palpableabdominal mass. Inguinal and/or supraclavicularlymphadenopathy is also a rare but possible presen-tation.28 A significant number of patients noticed anincrease in testicular size or vanishing testicularmass. A high degree of suspicion is needed to recog-nize the entity. Integrating information provided bytumor markers (AFP and �HCG) often after biopsyor retroperitoneal mass excision and testicular ul-trasound is crucial to make a prompt diagnosis thatallows a higher chance of cure. Tumors with worseprognosis are those with higher a tumor burden andnonseminomatous histology in metastases, espe-cially choriocarcinoma.

CONCLUSIONS

Retroperitoneal extragonadal germ cell neoplasmsare cancers of primary testicular origin that haveundergone different degrees of spontaneous regres-sion. Prognosis is serious enough to justify orchiec-tomy in each case and it appears critical to achieve acorrect diagnosis and prevent relapse after chemo-therapy. Characteristic ultrasound and histologicaltesticular findings may guide the diagnosis but ahigh degree of clinical suspicion is needed to diag-

nose the entity as early as possible.

1. Richie JP and Steele GS: Neoplasms of the tes-tis. In: Campbell’s Urology, 9th ed. Edited by AJWein, LR Kavoussi, AC Novick et al. Philadelphia:Saunders Elsevier 2007; vol 1, chapt 29, pp 893–935.

2. Llanes González L, Luján Galán M, RodríguezGarcía N et al: Tendencias en la incidencia decáncer testicular de células germinales en unárea sanitaria española de 300.000 habitantes(1991–2005). Actas Urol Esp 2008; 32: 691.

3. Fabre E, Jira H, Izard V et al: “Burned-out” pri-mary testicular cancer. BJU Int 2004; 94: 74.

4. Comiter CV, Renshaw AA, Benson CB et al:Burned-out testicular cancer. Sonographic andpathological characteristics. J Urol 1996; 156: 85.

5. Donderis Guastavino C, Boils Arroyo P, Blasco

��Burned-out��. Arch Esp Urol 1997; 50:196.

6. Ulbright TM, Amin MB and Young RH: Atlas ofTumor Pathology: Tumors of the Testis, Adnexa,Spermatic Cord and Scrotum, 3rd Series. Wash-ington, D.C.: Armed Forces Institute of Pathology1999; fascicle 25, pp 41–173.

7. López JI and Angulo JC: Burned-out tumour pre-senting as retroperitoneal choriocarcinoma. IntUrol Nephrol 1994; 26: 549.

8. International germ cell consensus classification:a prognostic factor-based staging system formetastatic germ cell cancers. International GermCell Cancer Collaborative Group. J Clin Oncol1997; 15: 594.

9. Prym P: Spontanheilung eines bosartigen, wahr-

metoses Gewachses

im Hoden. Virchows Arch [A] Pathol Anat Histol1927; 265: 239.

10. Azzopardi JG and Hoffbrand AV: Retrogression intesticular seminoma with viable metastases.J Clin Pathol 1965; 18: 135.

11. Coulier B, Lefebvre Y, de Visscher L et al: Me-tastases of clinically occult testicular seminomamimicking primary extragonadal retroperitonealgerm cell tumors. JBR-BTR 2008; 91: 139.

12. Scholz M, Zehender M, Thalmann GN et al: Ex-tragonadal retroperitoneal germ cell: evidence oforigin in the testis. Ann Oncol 2002; 13: 121.

13. Balzer BL and Ulbright TM: Spontaneous regres-sion of testicular germ cell tumors. An analysis of42 cases. Am J Surg Pathol 2006; 30: 858.

14. Ulbright TM: Germ cell tumors of the gonads: a

selective review emphasizing problems in dif-

REGRESSED TESTICULAR TUMORS2310

ferential diagnosis, newly appreciated, andcontroversial issues. Mod Pathol, suppl., 18:S61, 2005.

15. Munro AJ, Duncan W and Webb JN: Extrago-nadal presentations of germ cell tumours. Br JUrol 1983; 55: 547.

16. Krag Jacobsen G, Barlebo H, Olsen J et al:Testicular germ cell tumours in Denmark 1976 –1980. Pathology of 1058 consecutive cases. ActaRadiol Oncol 1984; 23: 239.

17. Powel S, Hendry WF and Peckham MJ: Occultgerm-cell testicular tumours. Br J Urol 1983; 55:440.

18. Henley JD, Young RH, Wade CL et al: Seminomaswith exclusive intertubular growth: a report of 12clinically and grossly inconspicuous tumors. Am J

EDITORIAL COMMENT

sound if there definite laterality of t

19. Bär W and Hedinger C: Comparison of histologictypes of primary testicular germ cell tumors withtheir metastases: consequences for the WHO andthe British Nomenclatures? Virchows Arch [A]Pathol Anat Histol 1976; 370: 41.

20. Utz DC and Buscemi MF: Extragonadal testiculartumour. J Urol 1971; 105: 271.

21. Burt ME and Javadpour N: Germ-cell tumours inpatients with apparently normal testes. Cancer1981; 47: 1911.

22. Simmonds PD, Mead GM, Lee AH et al: Orchiec-tomy after chemotherapy in patients with meta-static testicular cancer. Is it indicated? Cancer1995; 75: 1018.

23. Snow BW, Rowland RG, Donohue JP et al: Re-view of delayed orchiectomy in patients withdisseminated testis tumors. J Urol 1983; 129:

he metastatic

24. James PP and Mead GM: Sanctuary site relapsein chemotherapy-treated testicular cancer. AnnOncol 1992; 3: 41.

25. Greist A, Einhorn LH, Williams SD et al: Patho-logic findings at orchiectomy following chemo-therapy for disseminated testicular cancer. J ClinOncol 1984; 2: 1025.

26. Böhle A, Studer UE, Sonntag RW et al: Primary orsecondary extragonadal germ cell tumors? J Urol1986; 135: 939.

27. Mola Arizo MJ, Gonzalvo Pérez MD, TorregrosaMaicas MD et al: Tumor testicular bilateral “que-mado” (“burn out”). Actas Urol Esp 2005; 29: 318.

28. Kebapci M, Can C, Isiksoy S et al: Burned-outtumor of the testis presenting as supraclavicular

Surg Pathol 2004; 28: 1163. 522. lymphadenopathy. Eur Radiol 2002; 12: 371.

Specific histological changes in regressed tumorshave been described (reference 12 in article).Thus, testicular origin can be confirmed when rad-ical orchiectomy is performed. In the currentstudy 17 cases of presumed extragonadal primaryneoplasms were of testicular origin. It has beenour general practice to perform orchiectomy evenwhen a lesion is not specifically observed on ultra-

pattern in the retroperitoneum, especially if thesuspicious testis is atrophic and a normal con-tralateral testis is present. These authors providefurther confirmation that this is the appropriatemanagement.

Richard S. Foster

Department of UrologyIndiana University

Indianapolis, Indiana