The

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case records of the massachusetts general hospital

Founded by Richard C. Cabot
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Sally H. Ebeling, Assistant Editor
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Case 6-2007: A 28-Year-Old Man

with a Mass in the Testis
Donald S. Kaufman, M.D., Mansi A. Saksena, M.D., Robert H. Young, M.D.,
and Shahin Tabatabaei, M.D.

Pr e sen tat ion of C a se

From the Departments of Hematology
Oncology (D.S.K.), Radiology (M.A.S.),
Pathology (R.H.Y.), and Urology (S.T.),
Massachusetts General Hospital; and the
Departments of Medicine (D.S.K.), Radiology (M.A.S.), Pathology (R.H.Y.), and
Urology (S.T.), Harvard Medical School.
N Engl J Med 2007;356:842-9.
Copyright 2007 Massachusetts Medical Society.

842

A 28-year-old man was referred to this hospital for consultation on the management
of an enlarging testicular mass.
One year earlier, he had noticed a small, nontender mass in the posterior aspect
of the right testicle, which a physician, who was a relative of the patient, ascribed to
epididymitis; the mass seemed to disappear, or at least the patient did not notice it
again. One month before the consultation, the results of a routine annual physical
examination were normal; no abnormalities were noted in the testicles. Ten days
before the consultation, the right testicle became tender and began to enlarge
rapidly. The patient did not have fever or constitutional symptoms. His primary care
physician began treatment with levofloxacin. The results of laboratory studies
including urinalysis, complete blood count, platelet count, erythrocyte sedimentation
rate, and liver-, renal-, and thyroid-function tests were normal.
The testicular tenderness decreased, but the swelling persisted. One week later,
an ultrasound examination performed at another hospital showed a complex testic
ular mass that was considered highly suggestive of cancer. The patients physician
recommended an immediate biopsy of the testis, but the patient decided to come
to this hospital for a second opinion.
He felt well and had no constitutional, gastrointestinal, or urinary symptoms. He
had been in excellent health, had no allergies, and took no medications. He had
never had a urinary tract infection or epididymitis, and there was no history of inguinal hernia or sexually transmitted disease. He had never smoked; he occasionally
drank alcohol. He had married 4 months earlier and had no children. A grandfather
had died of pancreatic cancer, and a grandmother had cancer, but the patient did
not know the primary site. There was no family history of testicular or other genitourinary cancer.
On physical examination, the patient appeared well, although anxious. His vital
signs and the results of the general physical examination were normal; there was
no tenderness of the breasts or gynecomastia. The left testis was normal; the right
testis contained a firm, nontender mass, 4 cm in diameter. The epididymis was
normal. A specimen of blood was drawn to test for tumor markers.

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case records of the massachuset ts gener al hospital

Later that day, a diagnostic procedure was performed.

Differ en t i a l Di agnosis
Dr. Donald S. Kaufman: Dr. Saksena, will you review
the ultrasound study?
Dr. Mansi A. Saksena: The testicular ultrasound
study performed at the other hospital showed a
complex intratesticular mass, 3.1 by 2.9 cm, with
mixed cystic and solid components, within an en
larged right testis (Fig. 1). A Doppler study showed
minimal vascularity within the solid components
of the mass. The right epididymis and the left
testis and epididymis were normal.
Because the mass was intratesticular, the diagnosis of a hernia, varicocele, or scrotal hematoma
could be ruled out. Since the lesion was well defined, with normal adjacent testicular parenchyma, testicular torsion was unlikely. The age of the
patient and the ultrasonographic appearance of
the mass suggest that it is a testicular neoplasm.1
Dr. Kaufman: Dr. Tabatabaei, would you discuss
the differential diagnosis of a testicular mass
presenting as it did in this young man?
Dr. Shahin Tabatabaei: The patient presented to
his primary care physician with the relatively
abrupt onset of testicular pain and swelling and
a mass in the scrotum. Important factors to consider in formulating a differential diagnosis include the patients age; the rapidity of the onset
of symptoms; the presence or absence of pain,
fever, and local tenderness; and the results of the
physical examination. Scrotal masses may be due
to neoplasia, inflammation, or anatomical defects.
The differential diagnosis of a scrotal mass in a
young man such as this one includes testicular
cancer, hydrocele, spermatocele, inguinal hernia,
epididymo-orchitis, trauma, and epidermoid cyst.
Although benign scrotal masses are more common than malignant ones, it is crucial to rule out
the possibility of malignant causes before considering conservative management.
Most inflammatory scrotal masses are associated with scrotal pain, whereas noninflammatory
conditions, including testicular cancer, are more
often painless. However, acute pain occurs in
about 10% of patients with testicular tumors,
usually because of bleeding inside the tumor
or associated epididymitis that can cause acute
swelling and pain. Therefore, an acute presentation of testicular swelling and pain, as in this

Figure 1. Ultrasonographic Images of the Right Testis.

A transverse image through the right testicle (Panel A)
shows a complex intratesticular mass with a cystic
RETAKE (arrow).
1st
AUTHOR
Kaufman
ICM
component
(arrowhead)
and a solid component
2nd
REG Ftesticular
FIGURE tissue
1a&b is
of seen
2
Normal
along the anterior aspect
3rd
CASE
TITLE
of the
mass.
A Doppler image (Panel B) reveals
minimal
Revised
EMail
Line
4-C
vascularity in the solid component
(arrow).
Enon

ARTIST: mst

FILL

H/T
Combo

H/T

SIZE
16p6

AUTHOR, PLEASE NOTE:

been redrawn and type has been reset.

patient,Figure
doeshasnot
rule check
out the
diagnosis of testicuPlease
carefully.
lar cancer.
JOB:most
35608
ISSUE: 2-22-07
The
common inflammatory
cause of a
scrotal mass is epididymitis or epididymo-orchitis. This patient had noted a mass a year earlier
that was thought to be epididymitis. Considering
the relatively rapid growth of testicular germ-cell

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843

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tumors (doubling time of 10 to 30 days), it is unlikely that this mass was the initial manifestation
of a testicular cancer. Epididymo-orchitis is often
associated with systemic symptoms such as fever
and fatigue, as well as urinary symptoms, which
were not present in this patient. In rare cases,
sarcoidosis is manifested as a scrotal mass, but
the process is usually bilateral.
The clinical history is important, since conditions such as hydrocele and hernia often develop
gradually and are chronic, whereas a sudden onset would be more characteristic of infection or
torsion. Also important is a history of trauma,
which was not present in this case.
On physical examination, a hydrocele, sperma
tocele, or hernia would be fluctuant rather than
firm. Transillumination may help to differentiate
hernia from spermatocele or hydrocele. Epidermoid cysts are fixed to the skin. The presence of
localized tenderness of the epididymis, with or
without diffuse testicular swelling and tenderness, would suggest epididymitis or epididymoorchitis. Testicular cancers usually form a discrete,
firm, nontender mass within the testis; however,
the entire testis may be enlarged and, as in this
case, painful. A firm, nontender testicular mass
in a patient between the ages of 18 and 45 years
should be presumed to be malignant until proved
otherwise. In cases, such as this one, that pre
sent initially with diffuse testicular pain and swelling, the distinction between cancer and infection
may be difficult to make. In such a case, I feel
strongly that an immediate testicular ultrasound
study should be the next step. Although this examination may not be required in cases in which
the history and findings on physical examination
are typical, it can confirm the diagnosis in difficult cases and allows one to proceed with treatment right away. A trial of antibiotics, which is
often undertaken, as it was in this case, can lead
to an unacceptable delay in the diagnosis, especially if the patient is not compliant with followup. A delayed diagnosis of testicular cancer can
be associated with the finding of a later stage of
the disease at the time of diagnosis, and it may
affect the chance of cure.2,3 Reevaluation by the
patients physician 1 week later showed a persistent nontender mass. At this point, an ultrasound
examination was performed.
Dr. Kaufman: This patients physician advised a
testicular biopsy for diagnosis. The patient came
to see me 2 days later for a second opinion. Since
844

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testicular cancer seemed the most likely clinical

diagnosis, I recommended immediate radical orchiectomy, the procedure of choice for a suspected
testicular cancer. Blood was drawn for assessment
of tumor markers, the beta subunit of human
chorionic gonadotropin, and alpha-fetoprotein,
and the patient saw Dr. Tabatabaei later that day.
Dr. Tabatabaei: Testicular cancer is usually a
clinical diagnosis. The use of scrotal ultrasound
is merely confirmatory. This patients presentation
was very characteristic of a neoplastic process, so
Dr. Kaufman and I saw no need to wait for a
computed tomographic (CT) scan or for the results of tumor markers. Later that day, I performed
a right radical orchiectomy.

Pathol o gic a l Dis cus sion

Dr. Robert H. Young: The specimen was received for
intraoperative consultation. The testis contained
a mass that was obvious on palpation; sectioning
revealed a mass 4 cm in diameter with a variegated appearance, including yellow-to-white solid
areas, focal hemorrhage, and minor cystic areas
(Fig. 2A). The most likely diagnosis of a mass with
this appearance, particularly at this patients age,
is either pure embryonal carcinoma or a mixed
germ-cell tumor, which often has a component
of embryonal carcinoma. Seminoma is usually a
more uniform, creamy white neoplasm, although
it can exhibit hemorrhage or necrosis.4
On microscopical examination, the tumor was
largely an embryonal carcinoma, which is a prim
itive adenocarcinoma of the testis with papillary
(Fig. 2B), glandular, and solid patterns. The tumor
cells were highly malignant in appearance, with
pleomorphism and prominent nucleoli (Fig. 2C).
The papillary and overt glandular pattern rules
out a diagnosis of seminoma. There were minor
foci of yolk-sac tumor with a microcystic pattern
and teratomatous foci (Fig. 2D). Seminomas may
occasionally form spaces,5 but the appearance is
different from that of embryonal carcinomas. A
distinction between seminoma and embryonal
carcinoma can usually be made by evaluating
slides obtained routinely and stained with hematoxylin and eosin, but if indicated, immunohistochemistry may aid in the distinction, since embryonal carcinoma is negative for c-kit (CD117)
and positive for CD30, unlike seminoma.6
The tumor also had syncytiotrophoblastic giant
cells, which are common in embryonal carcinoma

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case records of the massachuset ts gener al hospital

Figure 2. Gross and Microscopical Features of the Testicular Tumor.

The sectioned surface of the testicular tumor shows mostly solid, yellow-to-white tissue, with focal hemorrhage and
a few cysts (Panel A). The tumor has the typical papillary (Panel B, hematoxylin and eosin) and glandular pattern of
1stpleomorphic nuclei and dusky
AUTHOR
Kaufman
embryonal carcinoma. A high-powerICM
view (Panel
C, hematoxylin
and eosin)RETAKE
shows the
2nd
F FIGURE
2a-d of 2 A teratomatous component
cytoplasm that are characteristic ofREG
embryonal
carcinoma.
(Panel D, hematoxylin and
3rd
CASE
TITLE
eosin) has squamous epithelium with keratin
production (left) and teratomatous
Revised glands (right).
EMail
Enon

ARTIST: mst

Line
4-C
SIZE
H/T
H/T
Combo
mor markers, 33p9
and

FILL
and sometimes lead to a misdiagnosis
of choriochest and abdominopelvic CT
NOTE:Dr. Saksena, will you describe the findcarcinoma. Many testicular tumors with AUTHOR,
a com- PLEASE
studies.
Figure has been redrawn and type has been reset.
ponent of embryonal carcinoma have at least
ings
on the postoperative abdominopelvic and
Please a
check
carefully.
minor teratomatous component. This very com- chest CT scans?
JOB: 35608
2-22-07
mon mixture of embryonal carcinoma
and teraDr.ISSUE:
Saksena:
Contrast-enhanced CT scanning of
toma was called teratocarcinoma in the older the abdomen, pelvis, and chest was performed
literature.
the day after surgery. There were no lung nodules
On microscopical examination, the tumor, or lymphadenopathy in the mediastinum, retroabout 60% of which was embryonal carcinoma, peritoneum, or pelvis.
was shown to be confined to the testis, without
Dr. Kaufman: Germ-cell tumors of the testis
any penetration of the tunica albuginea. There are uncommon but not rare. The usual age at the
was very focal vascular invasion.
time of diagnosis is 18 to 40 years, and these
tumors are the most common solid neoplasms in
men between the ages of 20 and 34 years. There
Dis cus sion of M a nage men t
are several histologic types of germ-cell tumors
Dr. Kaufman: In this case, the essential procedures and combinations thereof (Table 1). The Internaand tests for the clinical and pathological diag- tional Germ Cell Cancer Collaborative Group7
nosis and staging of a germ-cell tumor of the lists three prognostic categories good, intertestis included radical orchiectomy, tests for tu- mediate, and poor (Table 2) based on a com-

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bination of histologic features, site at presentation, stage, and tumor markers.

Testicular Cancer Staging

In addition to the tumornodemetastasis staging system for testicular neoplasms, the current
system includes a category for tumor markers
(Table 3).8 In this patient, the serum level of beta
human chorionic gonadotropin was 16 mIU per
milliliter (normal value, less than 5), and the
alpha-fetoprotein level was 10.5 ng per milliliter
(normal value, less than 6.1). The lactate dehydrogenase level was normal. On the basis of the size
of the tumor and the levels of tumor markers, the
tumor is stage IA, which falls into the good
prognostic group.
Treatment of Early-Stage, Nonseminomatous
Germ-Cell Tumors

Currently, there is controversy regarding the optimal treatment of stages IA, IB, and IIA testicular
cancers. It is generally agreed that stage IIB tumors
should be managed, at least initially, with chemotherapy. Radiation therapy, the treatment of choice
for patients with stage I seminoma, is not used in
the initial management of early-stage, nonseminomatous germ-cell tumors. Thus, the three adjuvant treatment options for this patient are active
surveillance, primary retroperitoneal lymph-node
dissection, and chemotherapy. All options result
in cure rates of 99% in cases such as this one, but
two thirds of patients are already cured after orchiectomy. Since all adjuvant treatments are associated with side effects, the goal is to provide
tailored adjuvant treatment for patients at high
risk for relapse and to avoid adjuvant treatment
for those at low risk for relapse.
Active Surveillance

Because patients with clinical stage I germ-cell

tumors have a 5-year survival rate that approaches 100%, some investigators have tried to reduce
the short-term and long-term toxicity of therapy,
including the elimination of a routine staging
retroperitoneal lymph-node dissection for selected patients. Surveillance (i.e., observation alone
after radical orchiectomy) is safe if the schedule
of laboratory tests, radiologic studies, and visits
to the physician is followed precisely. Although
the relapse rate is 20 to 30% among all patients
with clinical stage I, nonseminomatous germ-cell
tumors, more than 98% of these patients cancers
846

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Table 1. Germ-Cell Tumors of the Testis in Adults.*

Tumor Type

Approximate
Frequency
%

Seminoma
Nonseminomatous germ-cell tumor
Pure nonseminomatous germ-cell tumor
Embryonal carcinoma
Choriocarcinoma
Teratoma
Yolk-sac tumor
Mixed nonseminomatous germ-cell tumor
Embryonal plus other types

50
50
15
10
<1
35
<1
35
20

* Data are from Ulbright et al.4 Percentages in subcategories

are for the overall category.

are eventually cured.9 The advantage of surveillance is that at least 70% of patients do not need
any treatment after orchiectomy. One disadvantage is that up to 30% of patients must eventually
undergo four or more cycles of chemotherapy,
with the associated side effects. Furthermore, the
strict follow-up schedule may induce stress and
invite noncompliance.
Active surveillance protocols vary among institutions,10,11 but they typically include monthly
measurement of serum tumor markers and regular imaging studies for 2 years; I recommend
CT scanning of the chest and abdomen every
3 months. Since most relapses in patients with
nonseminomatous germ-cell tumors occur within
the first 2 years and are rare after 5 years, annual
surveillance is recommended after 5 years.
The patient under discussion is an excellent
candidate for active surveillance. His tumor markers fell to undetectable levels after orchiectomy,
his CT scan was normal, and compliance was
clearly not going to be a problem in obtaining the
necessary blood tests for tumor markers, chest
radiographs, and abdominal CT scans for the
duration of surveillance.9
Primary Retroperitoneal Lymph-Node Dissection

Among patients with stage I, nonseminomatous

germ-cell tumors who have no evidence of involvement of retroperitoneal lymph nodes on imaging studies, subsequent lymph-node dissection
shows positive nodes in about 30%. This procedure is an attractive alternative for patients who
may not be fully compliant with surveillance or

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case records of the massachuset ts gener al hospital

Table 2. Prognostic Factors and Survival among Patients with Nonseminomatous Testicular Germ-Cell Tumors.*
Good prognosis (56% of nonseminomatous germ-cell tumors)
Prognostic factors: testicular or retroperitoneal primary tumor, no nonpulmonary visceral metastasis, and low levels
of tumor markers (alpha-fetoprotein <1000 ng/ml, beta human chorionic gonadotropin <5000 IU/liter, and lactate
dehydrogenase <1.5 times ULN)
5-Year survival rate: progression-free, 89%; overall, 92%
Intermediate prognosis (28% of nonseminomatous germ-cell tumors)
Prognostic factors: testicular or retroperitoneal primary tumor, no nonpulmonary visceral metastases, and intermediate
levels of tumor markers (alpha-fetoprotein 1000 and 10,000 ng/ml, beta human chorionic gonadotropin 5000
and 50,000 IU/liter, lactate dehydrogenase 1.5 times and 10 times ULN)
5-Year survival rate: progression-free, 75%; overall, 80%
Poor prognosis (16% of nonseminomatous germ-cell tumors)
Prognostic factors: mediastinal primary tumor, nonpulmonary visceral metastasis, or high level of a tumor marker
(alpha-fetoprotein >10,000 ng/ml, beta human chorionic gonadotropin >50,000 IU per liter, or lactate dehydrogenase
>10 times ULN)
5-Year survival rate: progression-free, 41%; overall, 48%
* ULN denotes the upper limit of the normal range.

who would have difficulty with observation because their awareness that the surveillance approach carries a 30% risk of relapse and that a
relapse would require chemotherapy makes this
an unacceptable alternative. In a retrospective
comparison of retroperitoneal lymph-node dissection and surveillance for patients with clinical
stage I disease, the disease-specific survival rate
was greater than 98% for both options.12
A later clinical stage and the presence of persistently elevated serum tumor markers after orchiectomy are independent predictors of progression. In a study of patients with clinical stage I
to IIA disease and normal marker levels after
orchiectomy, the 4-year progression-free survival
rate after retroperitoneal lymph-node dissection
was 96%.13 This procedure represents an acceptable option for primary intervention in stages I
and IIA testicular germ-cell tumors. It is not in
dicated if tumor markers remain elevated after
the orchiectomy or if the clinical stage is IIB or
higher.
Retroperitoneal lymph-node dissection carries
a small risk of complications that can occur with
any major abdominal operation. In particular, this
procedure confers a risk of retrograde ejaculation
and subsequent infertility (a risk that can be reduced with nerve-sparing dissection) and smallbowel obstruction due to adhesions.

primary systemic chemotherapy as a means of

circumventing both retroperitoneal lymph-node
dissection and active surveillance. For patients
with disease that is stage IIB or higher and for
those with elevated tumor markers after orchiectomy, chemotherapy is the treatment of choice.
Cisplatin-based chemotherapy, a mainstay in
the primary treatment of germ-cell neoplasms of
the testis, is associated with complications that
include Raynauds phenomenon,14 peripheral neuropathy,15 nephropathy, and secondary leukemia.16
Most important, a number of studies have shown
an increased risk of cardiovascular disease among
long-term survivors of testicular germ-cell tumors
treated with cisplatin.17-22 Patients with testicular
cancer are typically young at the time of treatment and usually survive for many years. Thus,
the potential for serious late cardiovascular disease needs to be considered when deciding whether to use chemotherapy for testicular cancer and
when following patients who have received chemotherapy in the past.23
Because this patients tumor falls into a good
prognostic category and because of the risks associated with chemotherapy, I did not recommend
chemotherapy as an option.
Dr. Tabatabaei, would you advise doing a retro
peritoneal lymph-node dissection in this case?
Dr. Tabatabaei: The patient has clinical stage I
disease. Approximately 60% of his tumor was
Chemotherapy
embryonal carcinoma, and lymphovascular invaA third alternative for patients with early-stage sion was only focally present. Although stage I,
disease is a short course (one to three cycles) of nonseminomatous germ-cell tumors that are more
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Table 3. Staging System for Early-Stage Testicular Germ-Cell Tumors.*

Stage

Tumor

Node

Metastasis

Serum Tumor Markers

IA

T1

N0

M0

S0

IB

T2T4

N0

M0

S0

IIA

T2T4

N1

M0

S01

IIB

T2T4

N2

M0

S01

* Data are from Greene et al.8 Tumor stages are classified according to the criteria of the American Joint Committee on Cancer.
T1 indicates that the tumor is limited to the testis, without vascular invasion;
T2T4 indicates vascular invasion and involvement of the tunica vaginalis,
spermatic cord, or scrotum.
N0 indicates no evidence of a tumor in the lymph nodes; N1 a lymph-node
mass 2 cm or less in diameter or up to five positive nodes, each 2 cm or less
in diameter; and N2 a lymph-node mass more than 2 cm but not more than
5 cm in diameter, or more than 5 positive nodes with none more than 5 cm
in diameter, or evidence of extranodal extension of tumor.
M0 denotes no distant metastases.
S0 denotes normal levels of alpha-fetoprotein, beta human chorionic gonadotropin, and lactate dehydrogenase, and S1 the following levels: alpha-fetoprotein, less than 1000 ng per milliliter; beta human chorionic gonadotropin, less
than 5000 mIU per milliliter; and lactate dehydrogenase, less than 1.5 times
the upper limit of the normal range.

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undetectable 2 weeks after the orchiectomy. The

patient is therefore a good candidate for surveillance; chemotherapy can be used if he has a relapse. I would recommend retroperitoneal lymphnode dissection only if the tumor relapses and if
there are residual tumor masses after chemotherapy for relapsed disease.
Dr. Kaufman: We discussed the advantages and
disadvantages of retroperitoneal lymph-node dissection with the patient, but for a stage I tumor,
we preferred active surveillance, as did the patient. He was emphatically opposed to undergoing retroperitoneal lymph-node dissection and
highly committed to the strict regimen of followup required for active surveillance. He is being
followed at a cancer center in his home state,
with monthly assessment of tumor markers and
monthly chest radiographs. Eighteen months after the operation, he is well, with no evidence of
recurrence.

A nat omic a l Di agnosis

than 50% embryonal carcinoma and those with

lymphovascular invasion have each been reported Mixed germ-cell tumor (embryonal carcinoma,
to be associated with an increased risk of re- teratoma, and scant yolk-sac tumor).
lapse,10 in this case, the vascular invasion was
No potential conflict of interest relevant to this article was reminimal, and the levels of tumor markers were ported.
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Copyright 2007 Massachusetts Medical Society.

Lantern Slides Updated: Complete PowerPoint Slide Sets from the Clinicopathological Conferences
Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a teaching exercise or reference
material is now eligible to receive a complete set of PowerPoint slides, including digital images, with identifying legends,
shown at the live Clinicopathological Conference (CPC) that is the basis of the Case Record. This slide set contains all of the
images from the CPC, not only those published in the Journal. Radiographic, neurologic, and cardiac studies, gross specimens,
and photomicrographs, as well as unpublished text slides, tables, and diagrams, are included. Every year 40 sets are produced,
averaging 50-60 slides per set. Each set is supplied on a compact disc and is mailed to coincide with the publication of the
Case Record.
The cost of an annual subscription is $600, or individual sets may be purchased for $50 each. Application forms for the current
subscription year, which began in January, may be obtained from the Lantern Slides Service, Department of Pathology,
Massachusetts General Hospital, Boston, MA 02114 (telephone 617-726-2974) or e-mail Pathphotoslides@partners.org.

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