Artigo 2 - Seminoma Caso Clinico

Weekly Clinicopathological Exercises

F O U N D E D B Y R I C H A R D C . C A B O T

R

OBERT

E. S

CULLY

, M.D.,

Editor

E

UGENE

J. M

ARK

, M.D.,

Associate Editor

W

ILLIAM

F. M

C

N

EELY

, M.D.,

Associate Editor

S

ALLY

H. E

BELING

, L

UCY

D. P

HILLIPS

,

AND

S

TACEY

M. E

LLENDER

,

Assistant Editors

Volume 342 Number 2

·

115

Case Records of the Massachusetts General Hospital

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 1-2000

PREFACE

This millennial year is also a centennial year, andsince the Case Records were conceived about a cen-tury ago, it is fitting to recount the circumstances oftheir origin on the occasion of the first Case Recordof 2000. In its first issue of the 20th century, the

Boston Medical and Surgical Journal,

later to becomethe

New England Journal of Medicine,

published“The Case Method of Teaching Systematic Medi-cine” (1900;142:31-6), an article submitted by Wal-ter B. Cannon, a senior student at Harvard MedicalSchool who would later become the George Higgin-son Professor of Physiology at the medical school. Inthe article, Cannon wrote that continuous lecturingwas a “dreary and benumbing process.” Charles Wil-liam Elliot, Harvard’s president at the time and a lead-ing reformer of medical education, was greatly im-pressed, and with his enthusiastic support, the casemethod of teaching medicine rapidly became popular.

Meanwhile, Richard C. Cabot, an internist andprominent hematologist who had experimented withthe case method of teaching in student examinationstoward the end of the 19th century, began to use it inregular teaching exercises for third-year students in1900. Soon after he became an attending physicianat the Massachusetts General Hospital, he inaugurat-ed weekly clinicopathological conferences at the hos-pital with James Homer Wright, chief of the pathol-ogy laboratories. In 1915, Cabot began to have thecase discussions printed privately and distributed for$5 a year to any physician who requested them. Nineyears later, the first Case Records were published inthe

Boston Medical and Surgical Journal

(1924;191:30-9), and they have continued to appear in the

Journal

to this day, more than 5000 cases later.

R

OBERT

E. S

CULLY

, M.D.

PRESENTATION OF CASE

A 27-year-old man was admitted to the hospitalbecause of abdominal pain.

The patient had been well until the morning ofadmission, when he awoke with pain in the right low-er abdominal quadrant and lumbar region, accompa-nied by mild nausea. He had passed a normal stoolon the previous day. The pain became more severe,and he came to this hospital.

The patient had a depressive disorder, for which hetook clomipramine, but had otherwise been healthy.The only surgical procedure he had undergone wasa right inguinal herniorrhaphy performed at the age ofsix years. He had no history of injury, fever, diarrhea,hematochezia, dysuria, hematuria, or weight loss.

The temperature was 36.4°C, the pulse was 64,and the respirations were 18. The blood pressure was145/80 mm Hg. On examination, the patient was insevere pain. There was tenderness in the right lowerquadrant and right flank and over the right paraspi-nal muscles. The abdomen was soft, with normal bow-el sounds; no mass was palpated. The genitalia werenormal. There was no lymphadenopathy. A rectalexamination showed no abnormalities, and a stoolspecimen was negative for occult blood.

The urine was normal. The results of laboratorytests are shown in Tables 1 and 2. A computed tomo-graphic (CT) scan of the abdomen and pelvis (Fig. 1)showed a mass, 8 by 7 by 7 cm, that was of lower den-sity than the right psoas muscle. The mass had dis-placed and narrowed the inferior vena cava. On a mag-netic resonance imaging (MRI) scan of the pelvis (Fig.

T

ABLE

1.

H

EMATOLOGIC

L

ABORATORY

V

ALUES

.

V

ARIABLE

O

N

A

DMISSION

O

N

T

HIRD

H

OSPITAL

D

AY

Hematocrit (%) 42.7 36.3

Erythrocyte sedimentation rate (mm/hr) 11 48

White-cell count (per mm

3

) 10,500 13,100

Differential count (%)NeutrophilsBand formsMetamyelocytesLymphocytesMonocytesEosinophilsBasophils

8111

10331

80

Platelet count (per mm

3

) 265,000 229,000

Prothrombin time Normal

Partial-thromboplastin time Normal

Copyright © 2000 Massachusetts Medical Society. All rights reserved. Downloaded from www.nejm.org by JONATAS BERNARDES on January 2, 2010 .

116

·

Januar y 13, 2000

The New England Journal of Medicine

2), obtained after the administration of gadolinium,the retroperitoneal mass was anterior to the rightpsoas muscle and appeared to be separate from it andthe adjacent spine. On T

1

-weighted images, the signalintensity of the mass was the same as that of the mus-cle. On T

2

-weighted images, there was a heterogene-ous increase in the signal intensity of the mass, as wellas enhanced signal intensity in the adjacent retroperi-toneum, which was believed to reflect the presence ofedema. Peripheral enhancement with minimal centralenhancement, possibly caused by necrosis, was ob-served on T

1

-weighted and fat-saturated images ob-tained after the administration of gadolinium. A mag-netic resonance angiographic study showed narrowingof the inferior vena cava, which was patent. An abdom-inal and pelvic angiographic examination showed that

the inferior vena cava was patent but extrinsically com-pressed and displaced from the L3 level to that of L5;there was a partial right ureteral obstruction, withmild hydronephrosis.

Radiographs of the chest and lumbar spine werenormal. A CT scan of the thorax, obtained after theoral administration of contrast material, showed nolymphadenopathy or other evidence of tumor.

Clomipramine was continued; acetaminophen, me-peridine, hydroxyzine, and ketorolac were adminis-tered for pain relief. The temperature rose daily tothe range of 38.1° to 38.9°C. Cultures of blood andurine were sterile.

On the third hospital day, the urine was normal.The results of laboratory tests are shown in Table 1.A diagnostic procedure was performed.

*To convert the value for glucose to millimolesper liter, multiply by 0.05551.

T

ABLE

2.

B

LOOD

C

HEMICAL

V

ALUES

ON

A

DMISSION

.

V

ARIABLE

V

ALUE

Glucose (mg/dl)* 127

Protein (g/dl)AlbuminGlobulin

8.64.73.9

Lactate dehydrogenase (U/liter) 445

Other values Normal

Figure 1.

Abdominal CT Scan Showing a Right-Sided Retroperi-toneal Mass of Low Density Anterior to the Right Psoas Muscleand Medially Displacing and Narrowing the Inferior Vena Cava(Arrow).

Figure 2.

MRI Scan of the Abdomen.The mass has the same signal intensity as the right psoas mus-cle on the T

1

-weighted image (Panel A), but it has a hyperin-tense signal on the T

2

-weighted image (Panel B).

A

B



Volume 342 Number 2

·

117

DIFFERENTIAL DIAGNOSIS

D

R

. P

HILIP

W. K

ANTOFF

*: The most striking fea-tures of this case are the acute nature of the patient’sillness and his pain. The key finding on examinationis the retroperitoneal mass.

The radiographic findings are critical to the differ-ential diagnosis.

1-3

May we see the radiographs now?D

R

. C

ONSTANTINO

S. P

ENA

: The CT scan of theabdomen and pelvis (Fig. 1), obtained after the intra-venous administration of contrast material, shows aretroperitoneal mass, 8 by 7 by 7 cm, of lower densitythan the psoas muscle. The mass narrows and displacesthe inferior vena cava. An MRI scan of the abdomen(Fig. 2) confirms the presence of the mass, which hasa signal intensity equal to that of the psoas muscleon T

1

-weighted images and an increased signal inten-sity on T

2

-weighted images. The magnetic resonanceangiographic examination shows smooth, extrinsic an-terior compression of the inferior vena cava at the lev-el of the lower lumbar spine, with evidence of a partialright ureteral obstruction and mild hydronephrosis.

D

R

. K

ANTOFF

: The clinical and radiographic find-ings in this case can be explained by both benign andmalignant processes. The acute onset of pain is con-sistent with the presence of a hematoma, but the ab-sence of a history of trauma or a bleeding disordermakes this diagnosis unlikely. Furthermore, retroperi-toneal hematomas usually arise within the psoas mus-cle rather than adjacent to and distinct from it. Fi-nally, the signal intensity on MRI is inconsistent withthe presence of blood.

Infectious causes of the mass must be considered.If it is an abscess, a possible source of the infection isthe gastrointestinal tract. The patient’s age, his acutepresentation with pain in the right lower quadrant,and the location of the mass raise the question of ap-pendicitis with perforation and abscess formation. Al-ternatively, the source of infection could have been thegenitourinary tract or bone. The absence of strandingin the fat adjacent to the mass on CT studies makesan abscess an unlikely diagnosis. The absence of ear-lier gastrointestinal or genitourinary symptoms andthe normal, although limited, gastrointestinal find-ings also fail to support the diagnosis of an abscess.An abscess extending from bone, such as a tubercu-lous abscess, is unlikely, given the normal appearanceof the adjacent vertebral bodies and other bones, tothe extent that they can be seen radiographically.

If the mass is a neoplasm, the four leading diag-nostic possibilities are lymphoma, soft-tissue sarcoma,poorly differentiated carcinoma, and a germ-cell tu-mor. Lymphoma is a common type of malignant tu-mor in men in this patient’s age group.

4

Patientswith Hodgkin’s disease typically present with lym-

phadenopathy, usually with enlargement of one orseveral groups of lymph nodes. Constitutional symp-toms (so-called B symptoms), consisting of weightloss or fevers or both, may also be present. This pa-tient, however, had no history of these symptoms.Hodgkin’s disease that is exclusively subdiaphragmat-ic is more common in older adults, is usually bilateral,and in most cases also involves the iliac or inguinallymph nodes. None of these features are consistentwith this case. Furthermore, an elevation in the lactatedehydrogenase level similar to the elevated value inthis case is less commonly associated with Hodgkin’sdisease than with other tumors. Isolated retroperito-neal findings, as well as isolated lymph-node findingsat peripheral sites, are also rare in cases of non-Hodg-kin’s lymphoma. Atypical presentations may occur inpatients with human immunodeficiency virus (HIV)infection, but we are given no information about thispatient’s HIV status. When non-Hodgkin’s lymphomadevelops in the abdomen, mesenteric lymphadenop-athy is more common than retroperitoneal lymphad-enopathy. Although pain may occur in lymph nodesinvolved by Hodgkin’s disease after the ingestion ofethanol, the rapid expansion of a lymph node involvedby any type of lymphoma rarely causes pain.

Soft-tissue sarcomas may arise in the retroperito-neum.

5-7

In this case, the CT scan suggested that themass might have arisen from the psoas muscle, but theMRI scan, which has better resolution, shows thatthe mass is distinct from the muscle, making it un-likely that a soft-tissue sarcoma originated from it. Itis possible that the mass originated from the connec-tive-tissue elements in the retroperitoneum. The solid,complex nature of the mass and its apparent capsule,as visualized by MRI, are consistent with the pres-ence of a soft-tissue sarcoma or even a poorly differ-entiated liposarcoma, since the fat content may beminimal. However, evidence of necrosis and an ele-vated lactate dehydrogenase level are not usually as-sociated with an isolated retroperitoneal sarcoma. Fur-thermore, the presence of pain suggests that if thetumor had been a sarcoma, it would have been poorlydifferentiated and would probably not have had awell-delineated capsule.

Patients who have occult carcinomas in the gastro-intestinal or genitourinary tract or in a lung may pre-sent with distant lymph-node metastasis, but this pa-tient’s youth is evidence against these diagnoses. Theabsence of a history of cutaneous lesions makes thediagnosis of metastatic melanoma unlikely. Poorly dif-ferentiated midline carcinomas have been describedin a subgroup of patients, including young men. Asubstantial number of these tumors, however, weresubsequently shown to be germ-cell tumors.

8-11

Be-fore the development of modern immunohistochem-ical techniques, it was often difficult to distinguishgerm-cell tumors from poorly differentiated carcino-mas with a similar appearance. Germ-cell tumors were

*Director, Lank Center for Genitourinary Oncology, Dana–Farber Can-cer Institute; associate professor of medicine, Harvard Medical School —both in Boston.


118

·

Januar y 13, 2000


usually not associated with elevated serum levels ofthe beta subunit of human chorionic gonadotropinand alpha-fetoprotein, but they were distinguished byan excellent response to cisplatin-based combinationchemotherapy. Most germ-cell tumors can now beaccurately diagnosed with the use of immunohisto-chemical techniques to detect the beta subunit of hu-man chorionic gonadotropin, alpha-fetoprotein, andplacental alkaline phosphatase or with the use of chro-mosomal analysis or fluorescence in situ hybridizationfor the highly prevalent isochromosome-12p abnor-mality.

12,13

True poorly differentiated carcinomas re-main outside the germ-cell category and have a muchpoorer prognosis.

The most likely cause of the retroperitoneal massin this patient is a germ-cell tumor. Such tumors arethe most common neoplasms in adolescent boys andmen between the ages of 15 and 35 years. In this case,the mass could be a germ-cell tumor that metasta-sized from an occult testicular tumor, which might bedetectable only by ultrasonography.

14

Alternatively,the mass could be a primary retroperitoneal germ-celltumor. Although the vast majority of germ-cell tu-mors in males arise in the testes, 5 percent originateat extratesticular sites, including the precoccygeal area,the retroperitoneum, the mediastinum, and the pin-eal gland.

15

The strongest risk factor for testiculargerm-cell tumors is cryptorchidism,

16-19

which increas-es the risk by a factor of more than three, but only10 percent of testicular germ-cell tumors arise in cryp-torchid testes.

20

A weaker risk factor, according tosome but not all studies, is a history of an inguinalhernia, which this patient had during childhood.

16-19

The appearance of the retroperitoneal mass in thiscase, although heterogeneous on MRI, is homoge-neous on CT, a finding that is consistent with thepresence of either a seminoma or a nonseminomatousgerm-cell tumor. Seminomas are detected in patientswith an average age of 35 years, which is older thanthe average age at the time of the diagnosis of non-seminomatous germ-cell tumors. The acute onset ofpain in this patient may have been the result of therapid enlargement of the tumor, with necrosis. Al-though the elevated lactate dehydrogenase level is anonspecific finding, it is commonly associated withgerm-cell tumors, with a correlation between the de-gree of elevation and the bulk of the tumor. The on-set of fever with leukocytosis and a rise in the eryth-rocyte sedimentation rate suggests an inflammatoryreaction, perhaps related to tumor-induced necrosis.The fall in the patient’s hematocrit may reflect bleed-ing into the mass that occurred after the MRI, whichshowed no evidence of bleeding, was performed. Theabsence of additional lymphadenopathy and visceralinvolvement is not inconsistent with the diagnosis ofa germ-cell tumor, since the tumor is frequently con-fined to the retroperitoneum.

In this case, the beta subunit of human chorionic

gonadotropin and alpha-fetoprotein, the serum mark-ers of the tumor, should be measured, and an ultra-sonographic examination of the testes should beperformed.

21

Over 80 percent of nonseminomatousgerm-cell tumors are associated with elevated levelsof the beta subunit of human chorionic gonadotropinor alpha-fetoprotein, and approximately 10 percent ofseminomas are accompanied by an elevated level ofthe beta subunit of human chorionic gonadotropin.

22

Although increased levels of these markers are non-specific findings, a moderate elevation of either onestrongly supports the diagnosis of a germ-cell tumor.If the ultrasonographic examination shows an occulttesticular tumor, an inguinal orchiectomy is indicated.Since this patient’s genitalia were normal on physicalexamination, I believe a primary retroperitoneal germ-cell tumor is more likely than a primary testicular tu-mor, and I would perform a needle biopsy of the massto establish the diagnosis of a germ-cell tumor. A tis-sue specimen is obtained to confirm the diagnosis incases of this type unless the need for treatment is sourgent that a delay would be life-threatening. Al-though extragonadal, nonseminomatous germ-cell tu-mors in general are thought to be associated with apoorer prognosis than testicular germ-cell tumors, thepoorer prognosis is confined to the mediastinal sub-group of extragonadal tumors, which tend to be larg-er and on average less sensitive to chemotherapy.

23,24

Patients with nonseminomatous retroperitoneal germ-cell tumors have an excellent prognosis, as do patientswith testicular germ-cell tumors of the same histo-logic type.

23

Whether this patient’s tumor is a non-seminomatous germ-cell tumor or a seminoma, itslarge size warrants primary treatment with cisplatin-based chemotherapy. If a residual mass is demonstrat-ed radiographically after chemotherapy for a nonsemi-nomatous tumor, surgical resection is essential.

25

Incontrast, if a mass persists after the treatment of aseminoma, further therapy is usually not necessary.

25,26

D

R

. S

USAN

M. B

RIGGS

: This patient was referredon a Saturday at midnight with typical symptoms ofacute appendicitis, but I ordered a CT scan becausehe had a normal white-cell count, which is very un-usual in patients with acute appendicitis. It was un-clear whether the mass that was detected was relatedto the genitourinary tract or was a primary sarcoma.So we consulted both a urologist and an oncologist.

CLINICAL DIAGNOSIS

Retroperitoneal germ-cell tumor, ? primary.

DR. PHILIP W. KANTOFF’S DIAGNOSIS

Retroperitoneal germ-cell tumor, probably pri-mary seminoma.

PATHOLOGICAL DISCUSSION

D

R

. E

STHER

O

LIVA

: Fine-needle aspiration biop-sy of the retroperitoneal mass was performed. The



Volume 342 Number 2

·

119

specimen contained large neoplastic cells, occurringsingly and in very small groups, as well as lympho-cytes, on an extensively necrotic background (Fig. 3).The neoplastic cells had large nuclei that were roundor square and contained one or two prominent nu-cleoli and clear cytoplasm (Fig. 4). These findings arecharacteristic of seminoma.

D

R

. R

OBERT

E. S

CULLY

: Dr. Pena, will you showthe results of scrotal ultrasonography?

D

R

. P

ENA

: A hypoechoic mass and small foci ofcalcification are present in the right testis (Fig. 5).

D

R

. S

CULLY

: Dr. Smith, will you tell us about thesubsequent management of this case?

D

R

. M

ATTHEW

S

MITH

: The patient had normallevels of alpha fetoprotein and the beta subunit ofhuman chorionic gonadotropin. In cases of retroperi-toneal seminoma, I generally favor primary orchiec-tomy to establish the histologic diagnosis and excludethe possibility of nonseminomatous components, butbecause of this patient’s severe pain and the compres-sion of the inferior vena cava and right ureter, I choseto administer bleomycin, etoposide, and cisplatin be-fore performing an orchiectomy. He had a promptclinical and radiographic response to the chemother-

apy, although after three cycles, radiographic restagingrevealed a residual retroperitoneal mass, 4 cm in diam-eter. He was then treated with radiation therapy, anda right inguinal radical orchiectomy was performed.

D

R

. O

LIVA

: The testis, 3.7 by 2.2 by 1.2 cm, wasattached to a normal spermatic cord. Sectioning re-vealed a well-circumscribed, white-to-tan, homoge-neous, firm, nodular mass, 1.5 by 0.9 by 0.5 cm, nextto the tunica albuginea (Fig. 6). The adjacent testic-ular parenchyma appeared normal. Microscopical ex-amination of the mass revealed hyalinized scar tissuecontaining scattered chronic inflammatory cells (Fig.7); no evidence of tumor was found within the scar.The seminiferous tubules near the scar were hyalin-ized, and the interstitial tissue contained a patchy in-filtrate of lymphocytes. Elsewhere, the tubules werelined almost exclusively by Sertoli cells, with scatteredspermatogonia and thickening of the lamina propria(Fig. 8). An extensive search revealed no intratubulargerm-cell neoplasia or invasive germ-cell tumor. Thesefindings are consistent with the diagnosis of a retro-gressed, or burned-out, germ-cell tumor of the testis.

Approximately 1 percent of patients with germ-cell tumors present with retroperitoneal masses and

Figure 3.

Large Noncohesive Neoplastic Cells (Top) Mixed withLymphocytes (Bottom) on a Background of Necrotic Tumor(Hematoxylin and Eosin, ¬250).

Figure 4.

Nuclei of Tumor Cells Containing Prominent Nucleoli(Hematoxylin and Eosin, ¬600).


120

·

Januar y 13, 2000


Figure 5.

Ultrasonographic Image of the Right Testis Showinga Hypoechoic Mass (Arrow).

Figure 6.

Bisected Orchiectomy Specimen Containing a Well-Circumscribed, White-to-Tan, Homogeneous Nodule, 1.5 by 0.9by 0.5 cm, Juxtaposed against the Tunica Albuginea.

Figure 7.

Hyalinized Scar Tissue with Scattered Chronic Inflam-matory Cells (Hematoxylin and Eosin, ¬32).

clinically normal testes.

27

In rare cases, retroperitonealgerm-cell tumors arise from primordial germ cellsarrested during development in their migration to thetestis or from ectopic testicular tissue,

28,29

but mostof these tumors are now considered to be metastasesfrom testicular germ-cell tumors.

30

In contrast, me-diastinal and pineal germ-cell tumors are believed tobe primary tumors.

31

Any type of germ-cell tumor may be found in theretroperitoneum; seminoma is the most common,followed by embryonal carcinoma. The presence of

a specific type of metastatic germ-cell tumor in theretroperitoneum, however, does not indicate that thesame type of tumor is present in the testis if the tu-mor is metastatic.

In patients with retroperitoneal or disseminatedgerm-cell tumors, histologic studies of the testis showa palpable or occult germ-cell tumor, which may ormay not be of the same histologic type as the met-astatic tumor; intratubular germ-cell neoplasia

32,33; orin the absence of tumor, decreased spermatogenesis,peritubular or diffuse fibrosis, atrophy, calcification,and scar tissue.34-41

Intratubular germ-cell neoplasia includes an un-classified form in which cells indistinguishable fromseminoma cells are scattered along the tubular base-ment membranes, intratubular seminoma, intratubu-lar embryonal carcinoma,42 and microinvasive semino-ma.43-46 Finally, in some patients, a germ-cell tumorhas been detected in an apparently normal testis onclinical examination 5 months to 14 years after thetreatment of a retroperitoneal germ-cell tumor.27,37

Friedman and Moore30 reported that of 29 “pri-mary” retroperitoneal germ-cell tumors evaluated bythe Armed Forces Institute of Pathology between



Volume 342 Number 2 · 121

whether the mass also had a nonseminomatous com-ponent.

In the case of a pure seminoma, some oncologistswould resect the residual mass and others would useradiation therapy, but probably most oncologistswould observe it. There are no data from random-ized trials that prove that radiation therapy is bene-ficial; in fact, the best data suggest that it is not. Inthis patient’s case, because of the size of the residualmass and the possibility of a nonseminomatous com-ponent, I would have favored a retroperitoneal lymph-node dissection.

DR. SMITH: Since mature teratoma is resistant tochemotherapy, its absence in the orchiectomy spec-imen argues against the diagnosis of teratomatousmetastasis to the retroperitoneum.

The patient was well one year after the completionof the radiation treatment. CT scans of the abdomenand chest revealed no evidence of recurrent tumor.

DR. DONALD S. KAUFMAN: The lesson in thiscase is that the possibility of a germ-cell tumor mustbe considered when a mass is found, particularlywhen the patient is in this man’s age group, becausegerm-cell tumors are easily treated and are usuallycurable, unlike almost all other malignant tumors inthe differential diagnosis. Even if a testicular mass isabsent or the patient’s age is outside the usual agerange for testicular cancer, a germ-cell tumor mustbe ruled out.

ANATOMICAL DIAGNOSIS

Seminoma, retroperitoneal, consistent with retro-gressed testicular seminoma.

REFERENCES

1. Cohan RH, Baker ME, Cooper C, Moore JO, Saeed M, Dunnick NR. Computed tomography of primary retroperitoneal malignancies. J Comput Assist Tomogr 1988;12:804-10.2. Kutta A, Engelmann U, Schmidt U, Senge T. Primary retroperitoneal tumors. Urol Int 1992;48:353-7.3. Lane RH, Stephens DH, Reiman HM. Primary retroperitoneal neo-plasms: CT findings in 90 cases with clinical and pathologic correlation. AJR Am J Roentgenol 1989;152:83-9.4. Ampil FL. Malignant lymphoma presenting in the retroperitoneum. Oncology 1989;46:198-200.5. Heslin MJ, Lewis JJ, Nadler E, et al. Prognostic factors associated with long-term survival for retroperitoneal sarcoma: implications for manage-ment. J Clin Oncol 1997;15:2832-9.6. Lewis JJ, Leung D, Woodruff JM, Brennan MF. Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single in-stitution. Ann Surg 1998;228:355-65.7. McGrath PC. Retroperitoneal sarcomas. Semin Surg Oncol 1994;10:364-8.8. Greco FA, Hainsworth JD. Poorly differentiated carcinoma or adeno-carcinoma of unknown primary site: long-term results with cisplatin-based chemotherapy. Semin Oncol 1994;21:Suppl 12:77-82.9. Hainsworth JD, Wright EP, Johnson DH, Davis BW, Greco FA. Poorly differentiated carcinoma of unknown primary site: clinical usefulness of im-munoperoxidase staining. J Clin Oncol 1991;9:1931-8.10. Hainsworth JD, Johnson DH, Greco FA. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol 1992;10:912-22.11. Hainsworth JD, Greco FA. Treatment of patients with cancer of an un-known primary site. N Engl J Med 1993;329:257-63.12. Gibas Z, Prout GR Jr, Sandberg AA. Malignant teratoma of the testis

Figure 8. Seminiferous Tubules Lined Almost Exclusively bySertoli Cells, with a Thickened Lamina Propria (Hematoxylinand Eosin, ¬125).No intratubular germ-cell neoplasia is present.

1942 and 1946, 15 were found to be metastases fromclinically undetected testicular neoplasms. Eight of thetesticular neoplasms were burned-out tumors, whichwere characterized by scar tissue, with or without afew residual teratomatous elements or intratubulargerm-cell neoplasia in the adjacent testis. In the 1960s,Azzopardi and coworkers47,48 proposed that the tes-ticular scars resulted from necrosis and subsequentfibrosis of a tumor that had already metastasized asan extragonadal germ-cell tumor.

Although chemotherapy may eradicate an occulttesticular neoplasm, a high percentage of patients re-ceiving chemotherapy for metastatic disease have hadpersistent invasive or intratubular neoplasia on micro-scopical examination when the testis was subsequent-ly removed. For this reason, orchiectomy is recom-mended in all cases in which metastatic germ-celltumor has been treated initially.43,49

DR. KANTOFF: You seem to be confident, Dr.Smith, that the tumor is a seminoma. Only scar tis-sue was found in the testis, and the fine-needle aspi-ration specimen was a tiny sample of a large tumor.Although it was probably a seminoma, I wonder


122 · Januar y 13, 2000


with an isochromosome no. 12, i(12p), as the sole structural cytogenetic abnormality. J Urol 1984;131:762-3.13. Suijkerbuijk RF, Looijenga L, de Jong B, Oosterhuis JW, Cassiman JJ, Geurts van Kessel A. Verification of isochromosome 12p and identification of other chromosome 12 aberrations in gonadal and extragonadal human germ cell tumors by bicolor double fluorescence in situ hybridization. Can-cer Genet Cytogenet 1992;63:8-16.14. Horstman WG. Scrotal imaging. Urol Clin North Am 1997;24:653-71.15. Horwich A, Bajorin D. Testicular cancer: presentation, assessment and prognosis. In: Raghavan D, Scher HI, Leibel SA, Lange P, eds. Principles and practice of genitourinary oncology. Philadelphia: Lippincott-Raven, 1997:671-82.16. Moller H, Prener A, Skakkebaek NE. Testicular cancer, cryptorchi-dism, inguinal hernia, testicular atrophy, and genital malformations: case-control studies in Denmark. Cancer Causes Control 1996;7:264-74.17. Parker L. Causes of testicular cancer. Lancet 1997;350:827-8.18. Pinczowski D, McLaughlin JK, Lackgren G, Adami HO, Persson I. Occurrence of testicular cancer in patients operated on for cryptorchidism and inguinal hernia. J Urol 1991;146:1291-4.19. Prener A, Engholm G, Jensen OM. Genital anomalies and risk for tes-ticular cancer in Danish men. Epidemiology 1996;7:14-9.20. Swerdlow AJ. Epidemiology of testicular cancer. In: Raghavan D, Scher HI, Leibel SA, Lange P, eds. Principles and practice of genitourinary oncology. Philadelphia: Lippincott-Raven, 1997:643-52.21. Prow DM. Germ cell tumors: staging, prognosis, and outcome. Semin Urol Oncol 1998;16:82-93.22. Bower M, Rustin GJS. Serum tumor markers and their role in moni-toring germ cell cancers of the testis. In: Vogelzang NJ, Scardino PT, Ship-ley WU, Coffey DS, eds. Comprehensive textbook of genitourinary oncol-ogy. Baltimore: Williams & Wilkins, 1996:968-80.23. International Germ Cell Cancer Collaborative Group. International germ cell consensus classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 1997;15:594-603.24. Israel A, Bosl GJ, Golbey RB, Whitmore W Jr, Martini N. The results of chemotherapy for extragonadal germ-cell tumors in the cisplatin era: the Memorial Sloan-Kettering Cancer Center experience (1975 to 1982). J Clin Oncol 1985;3:1073-8.25. Einhorn LH. Do all germ cell tumor patients with residual masses in multiple sites require postchemotherapy resections? J Clin Oncol 1997;15:409-10.26. Puc HS, Heelan R, Mazumdar M, et al. Management of residual mass in advanced seminoma: results and recommendations from the Memorial Sloan-Kettering Cancer Center. J Clin Oncol 1996;14:454-60.27. Montague DK. Retroperitoneal germ cell tumors with no apparent testicular involvement. J Urol 1975;113:505-8.28. Meares EM Jr, Briggs EM. Occult seminoma of the testis masquerad-ing as primary extragonadal germinal neoplasms. Cancer 1972;30:300-6.29. Gross GW, Rohner TJ Jr, Lombard JS, Abrams CS. Metastatic semi-noma with regression of testicular primary: ultrasonographic detection. J Urol 1986;136:1086-8.

30. Friedman NB, Moore RA. Tumors of the testis: report on 922 cases. Mil Surg 1946;99:573-93.31. Comiter CV, Renshaw AA, Benson CB, Loughlin KR. Burned-out primary testicular cancer: sonographic and pathological characteristics. J Urol 1996;156:85-8.32. Daugaard G, von der Maase H, Olsen J, Rorth M, Skakkebaek NE. Carcinoma-in-situ testis in patients with assumed extragonadal germ-cell tumours. Lancet 1987;2:528-30.33. Chen KT, Cheng AC. Retroperitoneal seminoma and intratubular germ cell neoplasia. Hum Pathol 1989;20:493-5.34. Carroll PR, Whitmore WF Jr, Richardson M, et al. Testicular failure in patients with extragonadal germ cell tumors. Cancer 1987;60:108-13.35. Burt ME, Javadpour N. Germ-cell tumors in patients with apparently normal testes. Cancer 1981;47:1911-5.36. Bär W, Hedinger C. Ausgebrannte (okkulte) Hodentumoren: Hoden-läsionen bei klinisch scheinbar primär extratesticulären malignen Keimzell-tumoren. Virchows Arch [Pathol Anat] 1977;377:67-78.37. Munro AJ, Duncan W, Webb JN. Extragonadal presentations of germ cell tumours. Br J Urol 1983;55:547-54.38. Powell S, Hendry WF, Peckham MJ. Occult germ-cell testicular tu-mours. Br J Urol 1983;55:440-4.39. Buhtz P, Kaiper G. Spontaneous regression of germ cell tumors in tes-ticles. Pathol Res Pract 1995;191:630. abstract.40. Houston RR, Winter CC, Smith JP, Brenner MA. Primary retroperi-toneal seminoma without gonadal involvement: a report of 3 cases. J Urol 1971;106:841-4.41. Slater GS, Schultz H, Kreutzmann WB. Occult testicular tumor. JAMA 1955;157:911-2.42. Bohle A, Studer UE, Sonntag RW, Scheidegger JR. Primary or sec-ondary extragonadal germ cell tumors? J Urol 1986;135:939-43.43. Saltzman B, Pitts WR, Vaughan ED Jr. Extragonadal retroperitoneal germ cell tumors without apparent testicular involvement: a search for the source. Urology 1986;27:504-7.44. Wacksman J, Case G, Glenn JF. Extragenital gonadal neoplasia and metastatic testicular tumor. Urology 1975;5:221-3.45. Weaver DJ, Havey AD, Weinstein SH, Tully RJ. Nonpalpable occult testis tumor. Urology 1989;34:218-20.46. Salm R. Microscopic testicular teratoma with chorionepitheliomatous metastases. J Pathol 1972;108:91-4.47. Azzopardi JG, Mostofi FK, Theiss EA. Lesions of testes observed in certain patients with widespread choriocarcinoma and related tumors: the significance and genesis of hematoxylin-stained bodies in the human testis. Am J Pathol 1961;38:207-25.48. Azzopardi JG, Hoffbrand AV. Retrogression in testicular seminoma with viable metastases. J Clin Pathol 1965;18:135-41.49. Christensen TB, Daugaard G, Geertsen PF, von der Maase H. Effect of chemotherapy on carcinoma in situ of the testis. Ann Oncol 1998;9:657-60.

©2000, Massachusetts Medical Society.

35-MILLIMETER SLIDES FOR THE CASE RECORDS

Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a medical teaching exercise or

reference material is eligible to receive 35-mm slides, with identifying legends, of the pertinent x-ray films, electrocardiograms, gross

specimens, and photomicrographs of each case. The slides are 2 in. by 2 in., for use with a standard 35-mm projector. These slides,

which illustrate the current cases in the Journal, are mailed from the Department of Pathology to correspond to the week of

publication and may be retained by the subscriber. Each year approximately 250 slides from 40 cases are sent to each subscriber.

The cost of the subscription is $450 per year. Application forms for the current subscription year, which began in January, may be

obtained from Lantern Slides Service, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114 (telephone

[617] 726-2974). Slides from individual cases may be obtained at a cost of $35 per case.


New England Journal of Medicine

CORRECTION

Case Records of the Massachusetts General Hospital(Case 1-2000)

Case Records of the Massachusetts General Hospital (Case 1-2000)

. On page 116, in Figure 1, the arrow is misplaced. The corrected

figure and its legend are reprinted below.

Figure 1. Abdominal CT Scan Showing a Right-Sided Retroperi-

toneal Mass of Low Density Anterior to the Right Psoas Muscle and

Medially Displacing and Narrowing the Inferior Vena Cava (Arrow).

N Engl J Med 2000;342:1460


Artigo 2 - Seminoma Caso Clinico

Documents