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1698
RADIOLOGY-PATHOLOGY COLLECTION
Testicular Germ Cell Tumors:
Classification, Pathologic Features,
Imaging Findings, and Management
Venkata S. Katabathina, MD
Daniel Vargas-Zapata, MD
Roberto A. Monge, DO
Alia Nazarullah, MD
Dhakshina Ganeshan, MD
GENITOURINARY IMAGING |
Varaha Tammisetti, MD
Srinivasa R. Prasad, MD
Abbreviations: AJCC = American Joint Com-
mittee on Cancer, ESUR = European Society
of Urogenital Radiology, FDG = fluorodeoxy-
glucose, GCNIS = germ cell neoplasia in situ,
NSGCT = nonseminomatous germ cell tumors,
TGCT = testicular germ cell tumor, TM =
testicular microlithiasis, WHO = World Health
Organization
RadioGraphics 2021; 41:1698–1716
https://doi.org/10.1148/rg.2021210024
Content Codes:
From the Departments of Radiology (V.S.K.,
D.V.Z., R.A.M.) and Pathology (A.N.), Univer-
sity of Texas Health at San Antonio, 7703 Floyd
Curl Dr, San Antonio, TX 78229; Department
of Radiology, University of Texas M. D. Ander-
son Cancer Center, Houston, Tex (D.G., S.R.P.);
and Department of Radiology, University of
Texas Health at Houston, Houston, Tex (V.T.).
Presented as an education exhibit at the 2020
RSNA Annual Meeting. Received February 6,
2021; revision requested March 25 and received
April 29; accepted May 7. For this journal-based
SA-CME activity, the author V.S.K. has pro-
vided disclosures (see end of article); all other
authors, the editor, and the reviewers have dis-
closed no relevant relationships. Address cor-
respondence to V.S.K. (e-mail: katabathina@
uthscsa.edu).
©
RSNA, 2021
SA-CME LEARNING OBJECTIVES
After completing this journal-based SA-CME
activity, participants will be able to:
„ Explain normal germ cell development
in men and updates to pathogenesis in
the 2016 WHO classification system for
TGCTs.
„ Describe imaging findings of TGCTs,
with special emphasis on the role of im-
aging in staging and surveillance.
„ Discuss recent updates in the eighth
edition of the AJCC system for stag-
ing, treatment, and prognostication of
TGCTs.
See www.rsna.org/education/search/RG.
Testicular germ cell tumors (TGCTs) demonstrate a wide variety
of histopathologic, genetic, pathogenetic, and immunocytochemical
characteristics and various clinical-biologic profiles and prognoses.
Most TGCTs arise from an intratubular precursor cell referred
to as germ cell neoplasia in situ (GCNIS), which is an embryonic
germ cell with the potential to differentiate into a plethora of em-
bryonic and extraembryonic lineages. Advances in pathologic ex-
amination and genetics paved the way for the 2016 World Health
Organization (WHO) classification system, which recognizes two
pathogenetically distinct groups of TGCTs. Although postpuber-
tal tumors originate from GCNIS, almost all prepubertal tumors
belong to the non-GCNIS category. Molecular testing for chromo-
some 12p amplification helps to distinguish the two tumor catego-
ries. Imaging techniques such as US, CT, MRI, and fluorine 18
(18F)–fluorodeoxyglucose PET/CT are pivotal to the diagnosis and
staging, evaluation of complications and treatment response, and
long-term surveillance of TGCTs. In addition, select MRI findings
may help to differentiate a seminoma from a nonseminomatous
mixed TGCT. Accurate diagnosis of TGCTs has therapeutic and
prognostic implications. Although seminomas show exquisite re-
sponse to chemotherapy and radiation therapy, postpubertal tera-
tomas are highly resistant to both. The 2016 WHO classification
system introduced changes in the diagnosis and management of
TGCTs, including the development of new treatment and follow-
up guidelines. Radiologists play an essential role in the optimal
treatment of patients with TGCTs.
Online supplemental material is available for this article.
©
RSNA, 2021 • radiographics.rsna.org
Introduction
Testicular germ cell tumors (TGCTs), which are the most common
testicular neoplasms, commonly occur in young and middle-aged
men (1). TGCTs demonstrate diverse oncogenesis, pathologic find-
ings, and clinical-biologic behaviors. Evolving knowledge of genetics,
pathogenesis, and immunohistochemical markers of TGCTs led to
the updated 2016 World Health Organization (WHO) classification
system, which has substantial diagnostic and treatment implications
(2–5). A new term for the TGCT precursor lesion, germ cell neoplasia
in situ (GCNIS) was introduced, and two main categories of TGCTs
were defined: GCNIS-related and non–GCNIS-related tumors.
US, CT, MRI, and fluorine 18 (18F)–fluorodeoxyglucose (FDG)
PET/CT are important for diagnosis, staging, evaluation of compli-
cations, treatment follow-up, and long-term surveillance of TGCTs
(6–8). Also, MRI is useful in the differentiation of seminomas from
nonseminomatous mixed GCTs (NSGCTs)(9). Serum tumor mark-
ers including lactate dehydrogenase, α-fetoprotein, and β-human
RG • Volume 41 Number 6
TEACHING POINTS
„ GCNIS-related tumors include seminomas, embryonal carci-
nomas, postpubertal yolk sac tumors, teratomas, choriocar-
cinomas, NSGCTs, and “burned-out” TGCTs. Non–GCNIS-
related tumors include prepubertal teratomas, yolk sac tumors,
and spermatocytic tumors, which commonly affect older men.
„ US can help to differentiate seminomas from NSGCTs. Most
seminomas appear as well-circumscribed homogeneously hy-
poechoic masses. In comparison, nonseminomas tend to be
poorly defined heterogeneous masses with areas of necrosis,
hemorrhage, fibrosis, cystic change, and calcifications.
„ In 2015, the European Society of Urogenital Radiology (ESUR)
proposed a classification system for TM that was based on the
number of microliths per field of view at US and a summary
of management guidelines. TM is classified into three groups:
(a) limited TM, with less than five calcifications per view;
(b) classic TM, with greater than five calcifications per view;
and (c) diffuse TM, with multiple diffuse calcifications mani-
festing with a “snowstorm” appearance.
„ Enlargement and cystic changes in metastases, with interval
development of calcifications, osseous elements, and macro-
scopic fat, suggest the possibility of growing teratoma syn-
drome. Minimal or no uptake of FDG is seen at PET/CT.
„ Although conventional imaging practice is to measure lymph
nodes in the short-axis dimension for most cancers, National
Comprehensive Cancer Network guidelines and AJCC staging
systems recommend measuring lymph nodal metastases in the
greatest diameter of the lymph nodes in patients with testicular
cancer. Treatment strategies change depending on these values.
chorionic gonadotropin (β-hCG), are beneficial
in the management of TGCTs (10).The current
WHO classification system proposes new man-
agement and follow-up guidelines to improve the
overall prognosis of patients with TGCTs (11).
In this article, we review the 2016 WHO clas-
sification system for TGCTs, with attendant
implications for diagnosis, management, surveil-
lance, and prognosis, while highlighting changes
made in the eighth edition (2017) of the American
Joint Committee on Cancer (AJCC), tumor, node,
metastasis, and serum markers staging system.
Normal Germ Cell Development
in Men
Arrested germ cell development is an important
step in the development of TGCTs. Because the
pathogenesis of GCNIS-related TGCTs starts
before birth, understanding normal germ cell
development is imperative to comprehending
the pathogenesis of TGCTs (3). The gonocytes
or primitive germ cells with stem cell–like mark-
ers such as receptor tyrosine kinase (c-KIT )
and octamer binding transcription factors 3 and
4 (OCT3/4) may be identified at the bilaminar
disk stage of the embryo at approximately 2 weeks
of gestation. Primitive germ cells colonize the
testicular parenchyma after extensive migration
and, by puberty, lose the primitive markers to
Katabathina et al 1699
transform into mature sex cell progenitors (Fig 1)
(3). During migration, there is a hypothetical risk
of gonocytes being deposited along the pathway,
leading to the development of extragonadal GCTs
(12). Because of activation of the hypothalamic-
pituitary-gonadal axis at puberty, the gonocytes
enter meiosis, triggered by the loss of expression
of DMRT1 (sex-determining transcription factor),
and obtain a haploid genotype (3).
2016 WHO Classification of TGCTs:
What Is New?
Substantial advances in histopathologic, ge-
netic, and molecular findings have led to better
understanding of the pathogenesis of TGCTs,
which is reflected in the updated 2016 WHO
classification system (2,5). GCNIS was accepted
to replace prior misleading terms such as carci-
noma in situ, testicular intraepithelial neoplasm,
and intratubular germ cell neoplasia, unclas-
sified type. TGCTs were classified into two
main pathogenetically determined categories:
GCNIS-related tumors and non–GCNIS-related
tumors. GCNIS-related tumors typically occur in
men aged 18–45 years and are characterized by
chromosome 12p amplification. GCNIS-related
tumors include seminomas, embryonal carcino-
mas, postpubertal yolk sac tumors, teratomas,
choriocarcinomas, NSGCTs, and “burned-out”
TGCTs. Non–GCNIS-related tumors include
prepubertal teratomas, yolk sac tumors, and
spermatocytic tumors, which commonly affect
older men (2–5). Non-GCNIS TGCTs lack
chromosome 12p amplification (3,4) (Table
1). GCNIS expresses stem cell–like markers
(eg, OCT3/4 and c-KIT) and can accumulate
multiple mutations, eventually developing into
invasive malignancy (13,14). Spermatocytic
seminoma is now referred to as a spermatocytic
tumor on the basis of its indolent behavior, deri-
vation from mature germ cells, and absence of a
relationship to seminomas (2,5).
Pathogenesis of TGCTs
Abnormalities in germ cell development and
migration are thought to be the initiating factors
that contribute to the development of TGCTs.
Several risk factors have been identified, including
cryptorchidism, atrophic testis, hypospadias, family
history of a TGCT, low sperm count, testicular
dysgenesis syndrome, hereditary conditions such
as Cowden syndrome, and exogenous exposure
to estrogen (3,8,13,15). In a recent study, Nead
et al (16) has shown that exposure to diagnostic
radiation below the waist may increase the risk of
developing TGCTs. Reduction of medically unnec-
essary radiation to the testicles and optimization of
shielding practices are essential, when appropriate
1700 October Special Issue 2021 radiographics.rsna.org

Figure 1. Illustration shows the normal embryonic development and maturation of germ cells in men.

(16). The pathogenesis is different for the two types

Table 1: Current WHO Classification System
of TGCTs (Fig 2) (13,15). for TGCTs
Increased maternal estrogen levels from
exogenous exposure or multiple endogenous GCNIS-related TGCTs
hormone disrupters result in the arrest of fetal Seminomas
germ cells at the gonocyte stage. These ab- Nonseminomatous mixed germ cell tumors
normal gonocytes acquire multiple mutations   Embryonal carcinoma
during migration to the testicular parenchyma.    Yolk sac tumors, postpubertal type
Interaction of environmental factors and predis-    Teratomas, postpubertal type
posing conditions results in the development of    Choriocarcinomas and other trophoblastic
GCNIS (3,8,13,15). Arrested gonocyte devel- tumors
opment leads to the proliferation of the GCNIS Burned-out (regressed) germ cell tumors
due to pubertal activation of the hypothalamic- Non–GCNIS-related TGCTs
pituitary-gonadal axis. Chromosome 12p Yolk sac tumors, prepubertal type
amplification contributes to the invasiveness of Teratomas, prepubertal type and associated
TGCTs and is a hallmark feature of all GC- tumors
NIS-related TGCTs (3,8,13,15). Seminomas    Dermoid cysts
are the first tumors that develop from GCNIS    Epidermoid cysts
and exhibit hypomethylated chromatin and    Well-differentiated tumors
primitive stem cell–like markers (eg, commonly    Neuroendocrine tumors
OCT3/4)(3). Differentiation of seminoma cells Spermatocytic tumors
due to multiple epigenetic alterations leads to
other TGCTs, including choriocarcinomas that Sources.—References 2 and 5.
recapitulate extraembryonic tissues (ie, express
β-hCG), postpubertal yolk sac tumors that
express α-fetoprotein, and teratomas that are oblastoma occurring in the context of disorders
reminiscent of embryonic tissues (Fig 2) (3). of sexual development, GCNIS does not contrib-
In contradistinction, non-GCNIS tumors lack ute to pediatric GCTs (15). Prepubertal yolk sac
chromosome 12p amplification. Except for gonad- tumors are characterized by the loss of the tumor
RG • Volume 41 Number 6
Figure 2. Illustration shows the pathogenesis of TGCTs. Seminomas, embryonal carcinomas, choriocarcinomas, postpubertal yolk
sac tumors, and postpubertal teratomas develop from GCNIS and demonstrate isochromosome 12p. Prepubertal yolk sac tumors,
prepubertal teratomas and associated tumors, and spermatocytic tumors develop from normal germ cells, without GCNIS.
suppressor gene RUNX family transcription factor
3 (RUNX3) (13). Spermatocytic tumors dem-
onstrate recurrent amplifications of chromosome
9p (which contains a locus of the doublesex and
mab-3 related transcription factor 1 [DMRT1]
gene) (3,13,15).
Role of Imaging
Imaging is essential to diagnosis, staging,
surgical planning, and surveillance of TGCTs
(7,17,18). Although the final diagnosis of
TGCT is made at pathologic examination,
distinctive histologic features are reflected in im-
aging findings in selected patients (Tables 2, 3)
(7,17). Urologists expect to glean the following
information from radiology reports: (a) in the
primary tumor, potential clues to the histologic
diagnosis and involvement of the scrotal wall;
(b) metastases, including location, size, and
invasion into the adjacent structures; (c) follow-
up imaging studies for disease monitoring and
identification of complications; and (d) surveil-
lance, including evaluation of recurrent and
residual disease (7,17–19).
During assessment of a primary testicular
mass, radiologists may suggest potential his-
tologic diagnosis when it is possible to do so.
Katabathina et al 1701
Radiologists should be aware of the following
key concepts: (a) the presence of microlithiasis
in the adjacent testicular parenchyma suggests
the diagnosis of TGCT; (b) most seminomas
are homogeneous tumors, but heterogeneous
tumors correspond to NSGCTs; (c) a hetero-
geneous mass with cystic changes and calcifica-
tions suggests the possibility of a mixed NSGCT
with a postpubertal teratoma component;
(d) the presence of macrocalcifications and
hypoechoic areas at US in a young patient with
retroperitoneal lymphadenopathy is suspicious
for a “burned out” TGCT (a metastatic TGCT,
with spontaneous regression of the primary tu-
mor, without treatment); and (e) the presence of
“onion ring”calcifications is diagnostic of benign
epidermoid cysts (7,17).
Regarding staging and surveillance, the sites
and characteristics of metastases are related to
the histopathologic characteristics of the primary
tumor. For example, NSGCTs grow more rapidly
than do seminomas; visceral metastases occur
more frequently (>15%) with NSGCTs than with
seminomas (<5%) (19). Although the presence
of a hemorrhagic component is highly specific for
choriocarcinomas, teratomas are characterized by
cystic changes and calcifications (7,17).
1702 October Special Issue 2021 radiographics.rsna.org

Table 2: Imaging Findings and Features of GCNIS-related TGCTs

Type of TGCT Imaging Findings Features

Seminoma US: well-circumscribed homogeneously hypoecho-
ic mass with lobulated margins
MRI: T1-isointense and T2-hypointense mass,
with marked restricted diffusion
Embryonal carci- US: heterogeneously hypoechoic mass with ill-de-
noma fined margins and invasion of tunica albuginea
Postpubertal yolk US and MRI: ill-defined masses with varying
sac tumor amounts of cystic components from hemorrhage
and necrosis
Choriocarcinoma US: solid hypoechoic mass or heterogeneous mass
with hemorrhagic areas
CT: hypervascular metastases to the liver, lung
parenchyma, and retroperitoneal lymph nodes,
with spontaneous rupture
Postpubertal tera- US: well-circumscribed predominantly cystic le-
toma sion with macroscopic fat and calcifications
“Burned out” US: linear or nodular macrocalcifications, small
TGCT echogenic foci, focal hypoechoic areas with or
without calcifications, microlithiasis, and atro-
phic testis
Elevated serum lactate dehydrogenase
levels
Uniform cellular composition at patho-
logic evaluation
Poor prognosis with extratesticular
extension and metastases
Marked elevation of serum
α-fetoprotein levels
Marked elevation of serum β-hCG
levels
Aggressive tumor with worst prognosis
Microscopic vascular invasion leading
to early hematogenous spread
Normal serum tumor marker levels
Teratomas and choriocarcinomas com-
monly regress and form a fibrotic
scarlike area with calcifications

Table 3: Imaging Findings and Features of Non–GCNIS-related TGCTs

Type of TGCT Imaging Findings Features

Prepubertal tera- US: mature teratoma heterogeneously echogenic owing to Comprise 65% of all prepubertal
toma and asso- cystic lesions containing sebaceous fat tumors
ciated tumors* CT and MRI: macroscopic fat, calcifications, and cystic
components
Dermoid cyst at US: pilosebaceous component with no
other germ cell layer, cystic lesion with a thin wall and
a few septa
Epidermoid cyst at US: “onion ring” appearance, without
increased vascularity
Epidermoid cyst at MRI: T1 and T2 hyperintensity
Prepubertal yolk US: homogeneous solid hypoechoic mass that may Pure form is the most common
sac tumor involve the entire testicular parenchyma, or heteroge- testicular malignancy in chil-
neous mass with solid and cystic areas dren younger than 2 years
Elevated serum α-fetoprotein
levels
Spermatocytic US: well-circumscribed multinodular heterogeneous mass Rare tumor
tumor with cystic foci Occurs in older men
Normal serum markers
Metastases are rare
*Includes dermoid cysts, epidermoid cysts, well-differentiated tumors, and neuroendocrine tumors.

Imaging TGCTs with US TGCTs (Fig 3) (20). Also, US is helpful for

Color Doppler US is the imaging modality of
choice for the initial evaluation of scrotal masses
(20,21). US is helpful for differentiation of
testicular from extratesticular lesions and for
identification of undescended or malpositioned
testes in patients with cryptorchidism, micro-
lithiasis, small precursor lesions, and regressed
identification of cystic change, necrosis, and
calcifications in TGCTs. US is invaluable in the
evaluation of intra-abdominal or pelvic meta-
static disease and in identification of testicular
masses in young men with incidental retroperi-
toneal lymphadenopathy (20,22). US can help
to differentiate seminomas from NSGCTs.
RG • Volume 41 Number 6 Katabathina et al 1703

Figure 3. Undescended testis in a 12-year-old boy

with cryptorchidism. Gray-scale US image of the left
inguinal canal shows a hypoechoic oval structure (ar-
row) that is consistent with an undescended testis.

Figure 4. Differentiation of seminomas from NSGCTs. (A) Gray-scale US image of the scrotum in a 27-year-old man
shows a well-circumscribed homogeneously hypoechoic testicular mass (arrow) with associated microlithiasis (arrow-
head), which was proved to be a pure seminoma at pathologic examination. (B) Gray-scale US image of the scrotum in
a 32-year-old man shows an ill-defined heterogeneously mixed echogenic mass (arrow) with scattered anechoic areas
representing cystic or necrotic changes, which was proved to be an NSGCT composed of 45% postpubertal teratoma,
30% yolk sac tumor, 20% embryonal carcinoma, and 5% choriocarcinoma.

Most seminomas appear as well-circumscribed
homogeneously hypoechoic masses. In compari-
son, nonseminomas tend to be poorly defined
heterogeneous masses with areas of necrosis,
hemorrhage, fibrosis, cystic change, and calcifica-
tions (Fig 4) (6,20,23). Although internal tumor
vascularity is commonly seen in most tumors,
poorly vascularized tumors occasionally may be
misdiagnosed as segmental infarction or scarring
(23). US elastography and contrast-enhanced US
may be helpful in the assessment of testicular le-
sions and in the differentiation of malignant from
benign lesions (24,25).
Imaging TGCTs with CT
CT is the usual workhorse modality for staging,
treatment follow-up, assessment of complications,
and long-term surveillance of TGCTs (6,7,18).
Also, CT of the abdomen and pelvis is helpful to
identify malpositioned testes, metastatic retroper-
itoneal adenopathy, and emergency complications
such as urinary obstruction and hemorrhage (Fig
5) (6,7). Although chest radiography may suf-
fice for early-stage TGCTs, CT of the chest is
indicated for late-stage TGCTs with suspected
pulmonary metastases (26).
Imaging TGCTs with MRI
MRI is helpful in preoperative characteriza-
tion and staging of TGCTs, especially when
testicle-sparing surgery is planned (8,27). MRI
may allow differentiation of benign lesions from
TGCTs, thereby allowing unnecessary surgery to
be avoided (Fig 6) (27,28). Although diffusion-
weighted and contrast-enhanced MRI are com-
monly used, functional MRI techniques including
perfusion MRI, diffusion-tensor MRI, and MR
spectroscopy are being investigated for the charac-
terization of TGCTs (28). MRI has the potential
to help distinguish seminomas from NSGCTs
(9,29). Seminomas appear as unencapsulated tu-
mors that are isointense at T1-weighted MRI, with
homogeneous low signal intensity at T2-weighted
MRI. Fibrovascular septa manifest as hypointense
band-like structures at T2-weighted MRI, with
prolonged and more prominent enhancement (Fig
7) (9,29). In comparison, NSGCTs are markedly
heterogeneous with a hypointense pseudocapsule
1704 October Special Issue 2021 radiographics.rsna.org

Figure 5. CT evaluation of TGCTs. Coronal contrast-enhanced CT image of the

abdomen in a 28-year-old man shows bulky retroperitoneal lymphadenopathy,
with scattered hypoattenuating areas (arrow) and an ill-defined heterogeneous
lesion in the left hepatic lobe (arrowhead). Both of these lesions were proved to
be metastatic disease from a testicular NSGCT with predominant choriocarci-
noma components.

Figure 6. Testicular infarct in a 40-year-old man. (A) Gray-scale US image of the scrotum shows an ill-defined hypoechoic focal mass
(arrow) that is suspicious for a neoplasm in the right testicle. (B, C) Coronal T2-weighted (B) and gadolinium-enhanced T1-weighted (C)
MR images of the scrotum show a well-circumscribed wedge-shaped lesion that is hypointense (arrow in B) in the right testicular pa-
renchyma with mild contrast enhancement (arrow in C), which are findings that are suggestive of a testicular infarct, and this diagnosis
was subsequently proved at surgical excision.

at T2-weighted MRI. They may show heteroge-
neous areas at T1- and T2-weighted MRI that
are secondary to the presence of cystic change,
hemorrhage, or necrosis (Fig 7) (9,29). Zhang et
al (30) showed that a T2-weighted MRI-based ra-
diomics signature might allow noninvasive differ-
entiation of seminomas from NSGCTs (30). MRI
is also helpful for assessment of tumor extent,
including invasion of the adjacent structures, and
for detection of malpositioned testes in patients
with cryptorchidism (8,27). MRI is comparable to
CT for the identification of metastatic lymphade-
nopathy in TGCTs and for the effective detection
of residual or recurrent disease and distant metas-
tases, including intracranial metastatic disease and
complications (7,8,31).
Imaging TGCTs with 18F-FDG PET/CT
Although it is not commonly used, 18F-FDG
PET/CT helps to differentiate testicular ma-
lignancies from benign lesions and is used in
the posttreatment monitoring of select TGCTs
(7,32). Although PET/CT is useful in identify-
ing viable residual tumor in sites of metastasis
measuring larger than 3 cm after chemotherapy
in patients with seminomas, it is unreliable for
excluding viable tumor in NSGCTs (Fig 8)
(18,26,32,33). PET/CT should be performed at
least 6 weeks after chemotherapy to avoid false-
positive results from associated inflammation
(34). A PET/CT examination that is negative for
cancer after chemotherapy is reassuring. PET/
CT is recommended to identify early relapse in
patients with elevated serum marker levels and
normal CT examinations (18,26,33,34).
Testicular Microlithiasis
Testicular microlithiasis (TM) is the presence of
parenchymal calcifications (typically 2–3 mm in
size) in or outside the lumen of the seminiferous
RG • Volume 41 Number 6 Katabathina et al 1705

Figure 7. Differentiation of semi-

nomas from NSGCTs in two pa-
tients. (A–C) Pure seminoma
in a 27-year-old man. Axial T2-
weighted (A), diffusion-weighted
(b = 800 sec/mm2) (B), and gado-
linium-enhanced T1-weighted (C)
MR images of the scrotum show a
well-circumscribed homogeneous T2-
hypointense testicular mass (without
a discrete capsule) (arrow in A) that
demonstrates diffusion restriction (ar-
row in B) and relatively homogeneous
enhancement (arrow in C). This mass
was proved to be a pure seminoma at
radical orchiectomy. (D, E) NSGCT in
a 40-year-old man. Coronal T2-weighted (D) and gadolinium-enhanced T1-weighted (E) MR images of the scrotum show an
ill-defined hypointense mass arising from the right testicle that shows heterogeneous enhancement and extension into the
epididymis (arrow) and was proved to be an NSGCT at surgical resection.

Figure 8. Seminoma with viable tumor in the bilateral inguinal

lymph node, with metastases, in a 22-year-old man after he un-
derwent orchiectomy. Axial 18F-FDG PET/CT image shows areas of
substantially increased FDG uptake (arrows), which are suggestive
of viable tumors in the bilateral inguinal lymph nodes and were
proved at pathologic examination.

monly and is not required for diagnosis (Fig

tubules (20,35). Although TM is seen in greater
than 50% of patients with TGCTs, it can also be
seen in healthy men. The relationship between
these two entities is still controversial (20,35).
Studies (36–38) performed to evaluate TM as a
risk factor for TGCTs have shown ambiguous
results. Two large studies by Trout et al (37) and
Heller et al (38) demonstrated a strong associa-
tion between TM and TGCTs. Despite these re-
sults, currently there is no definitive evidence that
TM alone is a true premalignant condition. Cur-
rent guidelines reflect this philosophy (35,39).
At US, TM appears as distinct echogenic foci.
Posterior acoustic shadowing is not seen com-
9) (20,35). In 2015, the European Society of
Urogenital Radiology (ESUR) (39) proposed
a classification system for TM that was based
on the number of microliths per field of view at
US and a summary of management guidelines.
TM is classified into three groups: (a) limited
TM, with less than five calcifications per view;
(b) classic TM, with greater than five calcifica-
tions per view; and (c) diffuse TM, with mul-
tiple diffuse calcifications manifesting with a
“snowstorm” appearance (Fig 9) (39). Winter
et al (35) also proposed guidelines based on US
findings and associated risk factors for TGCTs.
Both guidelines suggest that the presence of TM
itself does not mandate regular surveillance, and
careful clinical correlation for associated risk
factors is required to make decisions on further
management (35,39). Although the presence of
risk factors for TGCTs may necessitate urologic
consultation and annual follow-up US up to
the age of 55 years, men with incidental, iso-
lated TM without a mass or risk factors should
1706 October Special Issue 2021
Figure 9. TM in three patients according to the ESUR classification system. (A) Gray-scale US image of the testicle shows only four
microliths per field of view (arrows), which is suggestive of limited TM. (B) Gray-scale US image of the testicle shows more than five
microliths per field of view (arrows), which is suggestive of classic TM. (C) Gray-scale US image of the testicle shows multiple micro-
liths per field of view (arrows) (ie, the “snowstorm appearance”), which is suggestive of diffuse TM.
be reassured and educated about the need for
monthly testicular self-examination (35,39).
GCNIS-related TGCTs
Germ Cell Neoplasia in Situ
GCNIS is found in the testicular parenchyma
adjacent to TGCTs in 90% of TGCTs and in the
contralateral testis in 4%–8% of TGCTs. Patients
with cryptorchidism or atrophic testis are at higher
risk for GCNIS and TGCTs (40). Approximately
70% of GCNIS-positive men may develop TGCT
within the next 7 years (13). Lenz et al (41)
showed that an irregular or coarse echogenic ap-
pearance of the testicular parenchyma at US may
suggest the possibility of GCNIS. However, this
finding has not been confirmed in larger studies.
The positive predictive value is low (22%). Cur-
rently, US has no role in screening for GCNIS.
Seminomas
Pure seminomas, which account for up to 50%
of TGCTs, commonly occur in men aged 30–40
years (42,43). Serum lactate dehydrogenase levels
are elevated in patients with seminomas, and
approximately 15% of patients may have a mildly
elevated β-hCG level because of the presence of
syncitiotrophoblastic cells (2,10,42). At patho-
logic examination, seminomas are usually solid
tumors with a pale tan slightly lobulated cut sur-
face. At histologic examination, a diffuse arrange-
ment of large polygonal cells that are divided into
large lobules by fibrous bands is a typical find-
ing (2,4,5). At immunohistochemical analysis,
seminoma cells stain positive for c-KIT, placental
alkaline phosphatase, and OCT3/4 (2,4,5).
The imaging appearance reflects the uniform
cellular composition of seminomas (43–45).
At US, seminomas typically are homogeneous,
hypoechoic, and solid appearing, with well-cir-
cumscribed or lobulated margins, and they show
increased vascularity along the fibrovascular septa
at Doppler US (Fig 10) (43,44). At MRI, semino-
mas are homogeneously T1 hypointense and T2
radiographics.rsna.org
hypointense, with well-circumscribed or lobulated
margins (9,29,43,46). At diffusion-weighted MRI,
marked restricted diffusion secondary to increased
cellularity and underlying inflammation can be
seen; bandlike hyperenhancement of fibrovascular
septa is characteristic of GCNIS (Fig 7) (9,43,46).
Nonseminomatous Germ Cell Tumors
NSGCTs comprise 30%–40% of all TGCTs and
may be pure or mixed tumors. Mixed tumors
show variable proportions of embryonal carci-
noma, yolk sac tumors, postpubertal teratomas,
and choriocarcinomas (2,5,42). NSGCTs are
diagnosed in men during the 3rd decade of life
(20,42). Unlike seminomas, NSGCTs manifest
with advanced disease in 60% of patients. The
prognosis is unfavorable for tumors with a higher
clinical stage (6,42). Imaging findings of NSGCTs
reflect their variegated nature and the proportion
of specific histologic types (Fig 11) (2,5,6). At
US, NSGCTs are typically heterogeneous; have
ill-defined margins; and contain cystic areas and
echogenic foci that correspond to necrosis, hemor-
rhage, and calcifications (Fig 11) (6,7,20,47).
Cysts within NSGCTs correspond to epithelium-
lined true cysts in teratomas and dilated rete testis
or necrosis in other tumors (20). The presence of
solid hypoechoic areas in NSGCTs commonly
corresponds to embryonal carcinoma and yolk sac
tumor components, whereas hemorrhagic areas or
metastases with hemorrhage indicate choriocarci-
noma (6,7,20,47). NSGCTs show heterogeneous
signal intensity at T1- and T2-weighted MRI, with
hemorrhage and necrosis. NSGCTs also show het-
erogeneous contrast enhancement and frequent in-
vasion of adjacent structures (Fig 7) (9,28,43,46).
Embryonal Carcinomas
Aggressive features such as extratesticular
extension and metastatic disease are common
in TGCTs that show embryonal carcinoma
(20,46). At histopathologic examination, ana-
plastic-appearing cells with diverse architectural
patterns are seen (2,4,5).
RG • Volume 41 Number 6 Katabathina et al 1707

Figure 10. Pure seminoma in a 35-year-old man. (A) Photograph of the sectioned gross specimen demon-
strates a testicular mass with a pale tan lobulated cut surface (arrows). (B) Photomicrograph shows nests of
large polygonal cells with moderate eosinophilic cytoplasms and prominent nucleoli (arrows) that are sepa-
rated by fibrous bands containing a lymphocytic infiltrate (arrowheads), which are consistent with a pure sem-
inoma. (Hematoxylin-eosin stain; original magnification, 320.) (C, D) Gray-scale (C) and color Doppler (D)
US images of the scrotum show a well-circumscribed lobulated homogeneously hypoechoic testicular mass
(arrow) with increased vascularity.

Figure 11. NSGCTs in three patients. (A–C) Pathologic findings of an NSGCT with a predominant yolk sac tumor and embryonal
carcinoma in a 26-year-old man. Photograph of the sectioned gross specimen (A) shows a discrete solid-cystic mass with areas of
hemorrhage and necrosis (arrow in A). Photomicrograph of the yolk sac tumor component (B) shows tumor cells palisading around
a central capillary, known as a Schiller-Duval body (arrow in B). (Hematoxylin-eosin stain; original magnification, 340.) Photomicro-
graph of the embryonal carcinoma component (C) shows a tubulopapillary appearance of cytologically anaplastic-appearing cells
(arrows in C). (Hematoxylin-eosin stain; original magnification, 340.) (D) Gray-scale US image of the right testicle in a 22-year-old
man with a pathologically proven NSGCT (mostly a mixture of embryonal carcinoma and postpubertal teratoma) shows an ill-defined
heterogeneously hypoechoic mass (arrow) replacing the entire testicular parenchyma. (E) Gray-scale US image of the left testicle in a
24-year-old man with a pathologically proven NSGCT (99% teratoma) shows a cystic mass (arrow) with thickened septa.
1708 October Special Issue 2021 radiographics.rsna.org

Figure 12. NSGCT with a predominant

embryonal carcinoma component in a
24-year-old man. Gray-scale US image of the
scrotum shows a lobulated heterogeneously
hypoechoic testicular mass (arrow) with in-
vasion of the adjacent tunica albuginea (ar-
rowhead). This mass was proved to be an
NSGCT with 95% embryonal carcinoma
and 5% postpubertal teratoma at pathologic
examination.

Figure 13. NSGCT with a predominant yolk sac tumor component in a 19-year-old man. (A) Gray-scale
US image of the scrotum shows a well-circumscribed hypoechoic testicular mass with scattered cystic areas
(arrow) and TM in the remaining testicle (arrowhead). (B) Axial contrast-enhanced CT image of the scrotum
shows a well-circumscribed heterogeneously enhancing mass in the right testicle (arrow). This mass was
proved to be an NSGCT with 99% postpubertal yolk sac tumor.

At US, embryonal carcinoma is a solid pre-
dominantly hypoechoic heterogeneous mass with
ill-defined margins, contour abnormality of the
testicle, and invasion of the tunica albuginea (Fig
12) (17,20). Ill-defined hypoechoic areas and
echogenic foci represent hemorrhage, necrosis,
and calcifications (20,43,48). At MRI, the tumor
shows heterogeneous signal intensity, with areas
of necrosis and hemorrhage (46,48).
Postpubertal Yolk Sac Tumor
A pure postpubertal yolk sac tumor in adults is
rare and is almost always part of an NSGCT.
The tumor demonstrates extraembryonic dif-
ferentiation into yolk sac elements and is com-
monly associated with marked elevation of serum
α-fetoprotein levels (5,10,48). At pathologic ex-
amination of gross specimens, the yolk sac tumor
component in an NSGCT appears as a solid to
cystic area with a gray to tan myxoid cut surface
and foci of necrosis and hemorrhage. Tumor cells
are positive for glypican-3 and α-fetoprotein at
immunohistochemical analysis (2,4,5).
At imaging, NSGCTs with a predominant
yolk sac tumor component may manifest as
ill-defined masses with varying amounts of
cystic change, indicating necrosis and echogenic
foci that correspond to hemorrhage (Fig 13)
(20,46,48). The tumor usually demonstrates
variable signal intensity at T1- and T2-weighted
MRI because of hemorrhage and cystic degen-
eration (28,46).
Choriocarcinoma
Up to 16% of NSGCTs show choriocarcinoma,
which is the most aggressive TGCT. The pure
form of this tumor is rare (20,48). Choriocar-
cinoma is associated with microscopic vascular
invasion, resulting in early widespread hema-
togenous dissemination. Serum β-hCG levels
are markedly elevated (10,48). The presence
of hemorrhagic nodules is typical at pathologic
examination of gross specimens. Extensive areas
of hemorrhage that are surrounded by a mixture
of trophoblasts with vascular invasion are seen
at histopathologic examination. Tumor cells are
positive for β-hCG and GATA binding protein
3 (GATA3) at immunohistochemical analysis
(Fig 14) (2,4,5).
At imaging, primary and metastatic masses are
hypervascular with central hemorrhagic necrosis
(20,46). Common metastatic sites at patient pre-
sentation include the lungs, liver, gastrointestinal
tract, and brain (46). At US, the primary testicu-
lar mass is solid, hypoechoic, and heterogeneous,
with cystic areas from hemorrhage and necrosis
RG • Volume 41 Number 6 Katabathina et al 1709

Figure 14. (A, B) Testicular choriocarcinoma in a 29-year-old man. (A) Photograph of pathologic specimens
shows a hemorrhagic tumor rimmed by a gray-tan area (arrows). (B) Photomicrograph shows large multi-
nucleated syncytiotrophoblasts and intermediate-sized cytotrophoblasts (arrows), with areas of hemorrhage
(arrowheads). (Hematoxylin-eosin stain; original magnification, 320.) (C, D) Choriocarcinoma in a 39-year-old
man. Gray-scale US image of the scrotum (C) shows an ill-defined heterogeneously hypoechoic mass with cystic
areas (arrows in C) that represent hemorrhage and necrosis. Axial contrast-enhanced CT image of the pelvis (D)
shows a large retroperitoneal lymph nodal mass (arrowheads in D) with heterogeneously enhancing areas in the
periphery and central necrosis, which are typical of choriocarcinoma metastases.

(Fig 14) (48). At CT and MRI, multifocal meta-
static masses are seen, with hypervascularity and
hemorrhagic necrosis (Fig 14) (46). TGCT with
substantial choriocarcinoma components has the
worst prognosis of all TGCTs and is rapidly fatal
if left untreated (42,48).
Postpubertal Teratoma
A pure teratoma is uncommon in postpubertal
male patients, and most tumors manifest as a
component of an NSGCT (5,42). Serum tu-
mor marker levels are normal (10). One-third of
patients present with advanced disease, includ-
ing mediastinal or intracranial masses, which are
associated with a higher incidence of recurrence
(42). At pathologic examination of gross speci-
mens, tumors are often solid to cystic masses,
with histologic features that vary depending on
the tissue types present (2,4,5).
Imaging shows predominantly cystic lesions
with macroscopic fat, calcifications, and solid
components, depending on their immaturity (Fig
15) (20,46,48). At US, these masses are mark-
edly heterogeneous and predominantly cystic
(20,48). Echogenic areas may correspond to
calcification, cartilage, immature bone, or macro-
scopic fat (20,48). At MRI, teratomas are well-
circumscribed complex cystic masses with signal
intensity that varies according to the contents of
the tumor (eg, serum, mucin, or keratin) (46).
Somatic-type malignancies that arise in the tera-
toma (ie, previously called teratocarcinomas) are
seen in approximately 3%–6% of teratomas. They
may arise in the testes or retroperitoneal lymph
nodes and are associated with a poor prognosis
(42). Sarcoma is the most common somatic-type
malignancy, the majority of which are rhabdo-
myosarcomas (42).
Burned-Out TGCTs
A burned-out TGCT is a metastatic TGCT in
which the primary tumor has completely or
partially regressed, forming a fibrotic scarlike
area. Burned-out TGCTs manifest exclusively by
means of metastasis, most commonly in the ret-
roperitoneum (2,49,50). Proposed mechanisms
include ischemic regression from rapid tumor
growth that exceeds perfusion and immune-
mediated regression (49,50). The most frequent
subtypes that regress are NSGCTs that predomi-
nantly contain teratomas or choriocarcinomas
(50). At pathologic examination, the regressed
1710 October Special Issue 2021 radiographics.rsna.org

Figure 15. Pure postpubertal teratoma in a 42-year-old man. (A) Gray-scale US image of the scrotum
shows a mixed solid and cystic testicular mass with a few punctate echogenic foci (arrow). (B) Axial
contrast-enhanced CT image of the abdomen shows a retroperitoneal lymph node with multiple calcifica-
tions (arrowhead). Postpubertal teratoma was diagnosed on the basis of pathologic examination.

Figure 16. Burned-out TGCT in three patients. (A) Photograph of the sectioned gross specimen in a young man (in his 20s) shows
the testicular parenchyma with a fibrotic scarlike area (arrow) and central calcification (arrowhead). (B) Gray-scale US image of the
scrotum in a 26-year-old man shows a focus of hyperechoic calcification (arrow) and an ill-defined hypoechoic area (arrowhead) with
predominant choriocarcinoma components. (C) Gray-scale US image of the right inguinal canal in a 17-year-old adolescent boy
shows an atrophic and undescended testicle with multiple hyperechoic calcifications (arrows).

areas show dense fibrosis with scar formation,
with or without tubular lithiasis, and lymphoplas-
macytic inflammation (Fig 16) (2,4,49).
US findings of a burned-out TGCT include
linear or nodular macrocalcifications, small
highly echogenic foci, focal hypoechoic areas
with or without calcifications, microlithiasis, and
atrophic testis (Fig 16) (6,49,50). At MRI, a focal
T2-hypointense area of architectural distortion
in the testicular parenchyma is seen without an
identifiable mass (6). CT and MRI demonstrate
retroperitoneal metastases and other metastases
(Fig E1) (49,50).
Non–GCNIS-related TGCTs
Prepubertal Teratoma and Associated
Tumors
Prepubertal teratomas and associated tumors
account for 65% of testicular tumors in prepu-
bertal children. They have an excellent prognosis
compared with that of postpubertal teratomas
(2,4,45). Dermoid cysts, epidermoid cysts, and
well-differentiated neuroendocrine tumors are
distinct types of prepubertal teratomas (2,4,45).
These tumors are also seen in adults, especially
epidermoid cysts. A prepubertal teratoma can be
mature or immature. Younger patients and those
with larger tumors and elevated α-fetoprotein
levels are more likely to have immature terato-
mas (51). At US, mature teratomas commonly
manifest as cystic lesions that contain sebaceous
material that contributes to a heterogeneously
echogenic appearance. Immature teratomas are
typically larger and solid from neuroectodermal
components. Imaging features may also change
over time (Fig 17) (45,51). CT and MRI can
show fat, calcification, and cystic components in
mature teratomas (45).
A dermoid cyst comprises a pilosebaceous
component with no other germ cell layer and
appears as a cyst with a thin wall at imag-
ing (45). An epidermoid cyst is a rare type of
monodermal teratomatous cyst that is lined with
a benign squamous epithelium that contains
keratin material (Fig 18) (20,45,52). At US,
epidermoid cysts show the characteristic “onion
ring” appearance, with alternating hypoechoic
and hyperechoic keratin layers and no color flow
at Doppler US (Fig 18) (20,47). Less-charac-
teristic imaging appearances at US include a
central hyperechoic area with a surrounding
RG • Volume 41 Number 6 Katabathina et al 1711

Figure 17. Prepubertal teratoma in a

9-year-old boy. Gray-scale US image of the
scrotum shows a well-circumscribed heter-
ogeneously echogenic mass with scattered
cystic areas (arrow), which was proved to
be a prepubertal teratoma at pathologic
examination.

Figure 18. Testicular epidermoid cysts in two patients. (A) Photomicrograph of a right testicular mass in a
33-year-old man shows a mature squamous epithelium–lined cyst (arrows) that is filled with acellular keratin
debris (arrowheads). (Hematoxylin-eosin stain; original magnification, 320.) (B) Gray-scale US image of the
scrotum in a 27-year-old man shows a right testicular mass with multiple concentric echogenic layers (arrow)
(ie, the classic “onion ring” appearance) from alternating hypoechoic and hyperechoic keratin layers in the
right testicle.

Figure 19. Atypical epidermoid cyst in a 31-year-old man. (A) Gray-scale US image of the scrotum shows a
mixed echogenic testicular mass with multiple circumferential calcifications (arrow). (B) Axial T1-weighted MR
image of the scrotum shows an ill-defined hyperintense focal mass in the left testicle (arrow), which was proved
to be an epidermoid cyst with atypical features at pathologic examination.

hypoechoic halo (ie, a “target” appearance), a Prepubertal Yolk Sac Tumors

well-circumscribed hypoechoic mass with rim
calcification, or an echogenic capsule (Fig 19)
(20,51,52). The appearance of these masses at
T1- and T2-weighted MRI is similar to that at
US, with an outer hypointense fibrous capsule,
dense central debris that is hypointense, and
mid-zone de­squamated cellular debris with
hyperintense high water and high lipid contents
(Fig 19) (52).
A pure form of prepubertal yolk sac tumor is the most
common testicular malignancy in children younger
than 2 years (45). Elevated serum α-fetoprotein
levels are seen and used for diagnosis and surveil-
lance (10,45). Tumors are histologically similar to
the postpubertal type, except for a lack of GCNIS
and the absence of regression (2,4,5).
At US, the prepubertal yolk sac tumor mani-
fests as either a homogeneous solid hypoechoic
1712 October Special Issue 2021 radiographics.rsna.org

mass that can involve the entire testicular pa-

renchyma or as a heterogeneous mass with solid
and cystic areas (Fig 20) (45). At MRI, the mass
is T2 hyperintense and T1 hypointense, with
restricted diffusion and heterogeneous contrast
enhancement (45).

Spermatocytic Tumors
A spermatocytic tumor is a rare TGCT (ie, it
represents only 1% of testicular cancers) that is
derived from mature germ cells such as a sper-
matogonium or an early spermatocyte. These
tumors rarely metastasize, and patients with them
have normal serum tumor marker levels (2,5).
In contradistinction to a seminoma, this tumor
Figure 20. Prepubertal yolk sac tumor in a 12-year-old boy.
manifests in men during the 6th decade of life Gray-scale US image of the scrotum shows an ill-defined het-
(43). At imaging, a spermatocytic tumor appears erogeneous mass with solid and cystic areas (arrow) that is
as a large (>5 cm) well-defined multinodular completely replacing the right testicular mass.
heterogeneous mass with cystic foci (43,46). It
has an excellent prognosis, without recurrence or
metastasis (43,46).

Complications of TGCTs
The complications of TGCTs include ureteral
obstruction, choriocarcinoma syndrome, growing
teratoma syndrome, testicular torsion, sarcoid-
like reaction, gynecomastia, and paraneoplastic
syndromes such as encephalitis (53). Metastatic
lymphadenopathy may cause ureteral obstruction,
which results in hydronephrosis and obstruction at
nephrography (Fig 21). Choriocarcinoma syn-
drome occurs in patients with metastatic chorio-
carcinoma. Spontaneous extensive bleeding from
hypervascular metastases results in diffuse alveolar
hemorrhage, hepatic subcapsular hematomas, and
hemoperitoneum (Fig 22) (53). Figure 21. Metastatic retroperitoneal lymphadenopathy in
Growing teratoma syndrome is an entity that a 20-year-old man with NSGCT causing substantial urinary
entails growth of NSGCTs, even after appropri- tract obstruction. Axial contrast-enhanced CT image of the
ate treatment with chemotherapy. Serum tumor abdomen at the level of the kidneys demonstrates retro-
peritoneal lymphadenopathy (arrow), resulting in moderate
markers are not elevated. This syndrome mimics hydronephrosis and decreased renal parenchymal enhance-
disease relapse or treatment failure because of the ment, which are suggestive of substantial urinary obstruc-
development of a mature teratoma in a preexisting tion (arrowheads).
metastasis (53). The initial NSGCT may or may
not contain a teratoma component. The treatment
of choice is surgical excision because chemother- Sarcoid-like reactions associated with TGCTs
apy is usually not effective (54). Enlargement and manifest as perihilar and mediastinal lymphade-
cystic changes in metastases, with interval devel- nopathy and perilymphatic pulmonary nodules.
opment of calcifications, osseous elements, and Similar findings may occur in the spleen or other
macroscopic fat, suggest the possibility of grow- lymph nodes (53,56). The sarcoid-like reaction
ing teratoma syndrome. Minimal or no uptake of may lead to confusion because it mimics progres-
FDG is seen at PET/CT (Fig 23) (53). sion of metastatic disease (53).
TGCTs may be associated with testicular tor-
sion in up to 6.4% of cases (55). An undescended Imaging Mimics and Pitfalls
testis is at higher risk for development of a TGCT, At US, numerous conditions may mimic a
and subsequent torsion in the abdominal or pelvic TGCT, including testicular hematoma, infarct,
cavity may cause substantial necrosis, which may abscess, adrenal rests (ie, congenital adrenal
manifest as a well-defined mass with intratumoral hyperplasia), lipomatosis (ie, Cowden syndrome),
necrosis and air at imaging (Fig 24) (6). sarcoidosis, splenogonadal fusion, metastases,
RG • Volume 41 Number 6 Katabathina et al 1713

Figure 22. Choriocarcinoma syndrome in a 25-year-old man. (A) Axial contrast-enhanced CT image of
the liver shows an ill-defined hypoattenuating liver lesion (arrow) with heterogeneous enhancement and a
left subcapsular hematoma (arrowhead) from spontaneous rupture of another left-lobe liver lesion (not shown).
(B) Axial CT image of the chest shows multiple metastatic nodules (arrowheads) in the bilateral pulmonary
parenchyma, with associated adjacent ground-glass attenuation that represents perilesional hemorrhage. These
findings are consistent with choriocarcinoma syndrome from a testicular choriocarcinoma.

testis (11,34,58). The extent of the disease and

Figure 23. Growing teratoma syndrome in
a 29-year-old man with a history of testicular
NSGCT after orchiectomy. Coronal contrast-
enhanced CT image of the abdomen shows a
large retroperitoneal multicystic mass with mul-
tiple enhancing septa and scattered calcified foci
(arrows). This mass was proved to be a mature
teratoma at pathologic examination and was
consistent with growing teratoma syndrome.
and lymphoma (Figs 6, E1–E5) (43). MRI may
be helpful in selected cases to differentiate TGCT
from other benign and malignant lesions. Ad-
vanced US such as US elastography or contrast-
enhanced US may improve the detectability of
tumors (Figs E2–E5) (24,57).
Management and Prognosis
Radical orchiectomy is the treatment of choice
for most TGCTs. Further treatment depends
on the pathologic diagnosis, disease stage, and
other risk factors (11,34). Testis-sparing surgery
may be a viable alternative to radical surgery in
patients with small testicular masses (ie, <2 cm),
bilateral TGCTs, and in a functionally solitary
postorchiectomy serum tumor marker levels (lac-
tate dehydrogenase, β-hCG, and α-fetoprotein)
help in the determination of the disease stage and
prognosis and provide guidance on treatment
decisions (11).
The eighth edition of the AJCC tumor, node,
metastasis, and serum markers system is cur-
rently used for staging TGCTs (34,59). The extent
of the local tumor is determined at pathologic
examination after orchiectomy, whereas imaging
studies are pivotal to node and metastasis stag-
ing (Table E1) (18,59). Although conventional
imaging practice is to measure lymph nodes in the
short-axis dimension for most cancers, National
Comprehensive Cancer Network guidelines and
AJCC staging systems recommend measuring
lymph nodal metastases in the greatest diameter of
the lymph nodes in patients with testicular cancer.
Treatment strategies change depending on these
values (18,34,59).
The eighth edition of the AJCC staging system
has introduced some important changes in the
tumor and metastasis aspects of staging TGCTs,
and treatment guidelines have changed accord-
ingly (18,59). Although the presence of enlarged
nonregional lymph nodes (eg, iliac, inguinal, and
pelvic nodes) and lung metastases are considered
M1a, distant metastases including nonpulmonary
visceral metastases and discontinuous spermatic
cord involvement are staged as M1b disease (59).
Depending on the pathologic diagnosis (eg, pure
seminoma vs NSGCT) and staging, multiple
treatment options exist, including surveillance,
retroperitoneal lymph node dissection, radiation
therapy, or cisplatin-based chemotherapy (11,34).
Current guidelines suggest that excision of
residual tumor be considered in masses that mea-
sure larger than 1 cm and that residual metastatic
1714 October Special Issue 2021
disease in the liver and the lungs requires detailed
description at imaging, because metastasectomy
is a surgical salvage option (19,34). Bleomycin-
related pulmonary toxicity usually manifests in
the first 3 years after chemotherapy; common
imaging findings are linear or nodular subpleural
basal predominant pulmonary lesions (19). De-
velopment of new venous or arterial thrombi and
plaques in the assessed vascular structures should
raise suspicion for potential cisplatin toxicity (19).
Novel targeted therapies, including antiangiogenic
agents such as pazopanib, sunitinib, and sorafenib,
and the immune checkpoint inhibitor pembroli-
zumab are being investigated in the treatment of
relapsed and refractory disease (8). Imaging has
an essential role in the surveillance and restag-
ing of TGCTs. Various surveillance protocols can
be used, depending on the stage, overall risk, and
treatment given (7,17).
The International Germ Cell Cancer Collabor-
ative Group (IGCCCG) established a consensus-
based prognostic classification system for germ
cell tumors in 1997 (60). In this risk-stratification
system, patient prognosis is categorized as good,
intermediate, or poor on the basis of the pri-
mary tumor location (eg, testis, retroperitoneal,
or mediastinal), postorchiectomy serum tumor
marker levels, and nonpulmonary metastases (60).
Primary tumor histologic examination and sites of
metastatic disease are the two most important de-
terminants of the prognosis, and imaging is crucial
to achieving good outcomes (19,61).
Intrathoracic metastases occur much more fre-
quently in NSGCTs than in seminomas. Although
seminomas disseminate through the thoracic duct
into the posterior mediastinum, NSGCTs usually
metastasize to the prevascular space or the pulmo-
nary hilar, supraclavicular, or cervical lymph nodes
(Fig E6) (19). Almost all intracranial metastases
are from NSGCTs (19). The presence of bone
metastases indicates aggressive behavior in both
seminomas and NSGCTs (19,61). Although the
overall prognosis of metastatic TGCTs has im-
proved in the last 20 years, the existing IGCCCG
classification system correctly stratifies the risk
(62). A new prognostic model for advanced
NSGCTs proposed by Gillessen et al (63) that
includes older age and lung metastases as negative
factors is being evaluated in larger studies. Emerg-
ing clinical, molecular, and immune-mediated
biomarkers are being developed as potential prog-
nostic indicators of TGCTs (64).
Future Directions
New molecular targets are currently being evalu-
ated for the diagnosis, treatment, prognostication,
and surveillance of TGCTs (14). Detection of
serum or semen microRNA such as miR-371–3 to
radiographics.rsna.org
Figure 24. Seminoma with torsion in a 49-year-old man with
an undescended testis. Axial contrast-enhanced CT image of
the abdomen shows a large well-circumscribed soft-tissue–at-
tenuation mass in the abdomen (arrow) with heterogeneous
hypoenhancement and multiple foci of air (arrowheads). At
surgical resection, this mass was proved to be a seminoma with
torsion and subsequent necrosis in an intra-abdominal testicle.
identify GCNIS and malignant TGCTs may fa-
cilitate early diagnosis and surveillance (13,14,65).
The CXC motif chemokine ligand 12 shows
promise for risk stratification and prognostication
for patients with stage I NSGCTs (66).Multiple
actionable targets including high-mobility group
protein 1 (HMGA1) pseudogenes, Aurora-B
serine-threonine kinases, and G protein-coupled
receptor 30 (GPR30) are essential in TGCT carci-
nogenesis (65).
Conclusion
TGCTs comprise a heterogeneous group of
testicular neoplasms with distinctive histogen-
esis, pathologic characteristics, and genetic
abnormalities. The fundamentals of embryologic
origins and the molecular underpinnings of many
TGCTs provide a basis for a better understand-
ing of distinct histopathologic factors, biomarkers,
and diverse tumor biologic characteristics. The
pathogenetically derived 2016 WHO taxonomic
system divides TGCTs into GCNIS-related and
non–GCNIS-related tumors. Imaging is a critical
component of the diagnosis, staging, and surveil-
lance of TGCTs. Novel molecular and imaging
biomarkers are under investigation for assessment
of treatment response, prognosis, and surveillance
of TGCTs.
Disclosures of Conflicts of Interest.—V.S.K. Activities related
to the present article: editorial board member of RadioGraph-
ics (not involved in the handling of this article). Activities not
related to the present article: disclosed no relevant relationships.
Other activities: disclosed no relevant relationships.
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