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MULTISYSTEM RADIOLOGY
Tuberous Sclerosis: Current Update
Mindy X.Wang, MD
Nicole Segaran
Sanjeev Bhalla, MD
Perry J. Pickhardt, MD
Meghan G. Lubner, MD
Venkata S. Katabathina, MD
Dhakshinamoorthy Ganeshan, MD
Abbreviations: AML = angiomyolipoma,
LAM = lymphangioleiomyomatosis, MMPH =
multifocal micronodular pneumocyte hyper­
plasia, mTOR = mammalian target of rapamy­
cin, PEComa = perivascular epithelioid tumor,
RCC = renal cell carcinoma, SEGA = subepen­
dymal giant cell astrocytoma, TSC = tuberous
sclerosis complex
RadioGraphics 2021; 41:1992–2010
https://doi.org/10.1148/rg.2021210103
Content Codes:
From the Department of Diagnostic Radiology,
University of Texas MD Anderson Cancer Cen­
ter, Pickens Academic Tower, 1400 Pressler St,
Unit 1473, Houston, TX 77030-4009 (M.X.W.,
D.G.); Department of Radiology, Mayo Clinic
Arizona, Scottsdale, Ariz (N.S.); Mallinckrodt
Institute of Radiology, Section of Abdomi­
nal Imaging, Washington University School of
Medicine, St Louis, Mo (S.B.); Department
of Radiology, University of Wisconsin School
of Medicine and Public Health, Madison, Wis
(P.J.P., M.G.L.); and Department of Radiology,
University of Texas at San Antonio, San Antonio,
Tex (V.S.K.). Presented as an education exhibit
at the 2020 RSNA Annual Meeting. Received
April 3, 2021; revision requested April 30 and re­
ceived June 7; accepted June 18. For this journal-
based SA-CME activity, the authors S.B., P.J.P,
M.G.L., and V.S.K. have provided disclosures
(see end of article); all other authors, the edi­
tor, and the reviewers have disclosed no relevant
relationships. Address correspondence to
M.X.W. (e-mail: Mindy.X.Wang@uth.tmc.edu).
©
RSNA, 2021
SA-CME LEARNING OBJECTIVES
After completing this journal-based SA-CME
activity, participants will be able to:
„ Recognize the major and minor diag­
nostic features of TSC.
„ List characteristic TSC-related imaging
manifestations.
„ Describe how genetic testing in TSC
can help predict the diagnosis.
See rsna.org/learning-center-rg.
Tuberous sclerosis complex (TSC) is a relatively rare autosomal
dominant neurocutaneous disorder secondary to mutations in the
TSC1 or TSC2 tumor suppressor genes. Although manifestation of
the classic triad of seizures, intellectual disability, and facial angio­
fibromas may facilitate timely diagnosis of TSC, the multisystem
features that may indicate TSC in the absence of these manifesta­
tions remain highly variable. In addition, patients with TSC are at
risk of developing multiple benign and malignant tumors in various
organ systems, resulting in increased morbidity and mortality. Thus,
imaging plays a critical role in diagnosis, surveillance, and manage­
ment of patients with TSC. It is crucial that radiologists be familiar
with TSC and the various associated imaging features to avoid a
delayed or incorrect diagnosis. Key manifestations include cortical
dysplasias, subependymal nodules, subependymal giant cell astro­
cytomas, cardiac rhabdomyomas, lymphangioleiomyomatosis, and
angiomyolipomas. Renal angiomyolipomas in particular can mani­
fest with imaging features that mimic renal malignancy and pose
a diagnostic dilemma. Other manifestations include dermatologic
and ophthalmic manifestations, renal cysts, renal cell carcinomas,
multifocal micronodular pneumocyte hyperplasia, splenic hamarto­
mas, and other rare tumors such as perivascular epithelioid tumors.
In addition to using imaging and clinical features to confirm the
diagnosis, genetic testing can be performed. In this article, the mo­
lecular pathogenesis, clinical manifestations, and imaging features
of TSC are reviewed. Current recommendations for management
and surveillance of TSC are discussed as well.
©
RSNA, 2021 • radiographics.rsna.org
Introduction
Tuberous sclerosis complex (TSC), also known as Bourneville dis­
ease, is a heritable neurocutaneous disorder or phakomatosis that is
characterized by multisystem involvement with development of mul­
tiple hamartomatous tumors. The classic clinical triad (ie, Vogt triad)
comprises seizures, intellectual disability, and facial angiofibromas;
however, this triad is seen in less than 50% of cases. Multisystem
clinical manifestations can vary substantially, even between closely
related individuals, making it challenging to diagnose this disorder
(1). Comprehensive evaluation of the clinical features of TSC in
conjunction with radiologic assessment is critical for diagnosis and
management.
Key manifestations include cortical dysplasias, subependymal nod­
ules, subependymal giant cell astrocytomas (SEGAs), cardiac rhabdo­
myomas, lymphangioleiomyomatosis (LAM), and angiomyolipomas
(AMLs), which are considered major clinical features of TSC (1).
Other manifestations include dermatologic and ophthalmic manifesta­
tions, renal cysts, renal cell carcinomas (RCCs), multifocal micronodu­
lar pneumocyte hyperplasia (MMPH), splenic hamartomas, and other
RG • Volume 41 Number 7
TEACHING POINTS
„ Major causes of death related to TSC include sudden death
from epilepsy; LAM; and renal complications, including mas-
sive hemorrhage from AML and renal failure.
„ Genetic linkage is related to loss-of-function germline muta-
tions in the tumor-suppressor gene TSC1 or TSC2.
„ There are four classic central nervous system findings associ-
ated with TSC: cortical and subcortical tubers, cerebral white
matter heterotopia, subependymal nodules, and SEGAs.
Central nervous system manifestations account for the major
causes of morbidity and mortality among persons with TSC,
occurring in more than 80% of these individuals.
„ When both LAM and AML are present, other TSC features
must be present for a definite diagnosis of TSC, as sporadic
LAM can often be seen in combination with renal AMLs.
„ Renal AMLs represent the second most frequent cause of mor-
bidity among patients with TSC owing to the risk of spon-
taneous hemorrhage and rupture. Such complications occur
increasingly with AMLs that are larger than 4 cm or with those
that are associated with aneurysms larger than 5 mm. If either
of these criteria is met, embolization or nephron-sparing sur-
gery is highly recommended.
rare tumors such as perivascular epithelioid tumors
(PEComas). While advances in management of
TSC have been made, the associated prognosis
remains poor, with the median patient age at death
being approximately 33 years (2). Major causes
of death related to TSC include sudden death
from epilepsy; LAM; and renal complications,
including massive hemorrhage from AML and
renal failure (3).
In this article, we review the molecular patho­
genesis, clinical manifestations, imaging features,
and current recommendations for management
and surveillance of TSC. Management and
surveillance recommendations from the 2012
International TSC Consensus Group are high­
lighted (1,4).
Genetics and Molecular Pathogenesis
TSC is an autosomal dominant disorder with a
highly variable phenotype and a relatively rare
estimated prevalence: one in 10 000 persons (5).
Two-thirds of cases are sporadic and secondary
to de novo mutations (5,6). Genetic linkage is
related to loss-of-function germline mutations in
the tumor-suppressor gene TSC1 or TSC2. The
TSC protein complex TSC1 at the 9q32 locus
encodes hamartin, while TSC protein complex
TSC2 at the 16p13.3 locus encodes tuberin. The
hamartin-tuberin complex is involved in many
pathways, including those involving cell growth,
cell proliferation, intracellular trafficking, cell ad­
hesion, and cell migration. This complex inhibits
the mammalian target of rapamycin (mTOR)
complex 1, which is essential in controlling cell
growth (5). Therefore, alterations in the func­
Wang et al 1993
tion of hamartin and/or tuberin lead to enhanced
stimulation of cell growth.
TSC2 mutations occur in 70% of individuals
with TSC, while TSC1 mutations occur in 20%
of these individuals (7). In about 10% of pa­
tients with this disorder, a pathogenic TSC gene
mutation may not be identified at conventional
testing, but next-generation sequencing may
reveal mosaic and intronic mutations in TSC1
or TSC2 (8). TSC2 mutations are associated
with more severe manifestations than are TSC1
mutations, presumably owing to the increased
rate of germline and somatic mutations in TSC2
as compared with the rates of these mutations in
TSC1 (9). TSC1 mutations are more often seen
in familial cases than in sporadic new cases. The
Knudson two-hit tumor-suppressor gene model
applies to TSC, as inactivation of both alleles of
either TSC1 or TSC2 leads to TSC manifesta­
tions, particularly AMLs, cardiac rhabdomyomas,
SEGAs, and LAM (9). Most mutations occur by
way of large deletions.
Diagnostic Criteria
In 2012, the International TSC Consensus
Group updated the diagnostic criteria for TSC to
include mutation analysis results and improved
identification of clinical features (1). According
to these criteria, identification of a pathogenic
mutation of TSC1 or TSC2 constitutes a definite
diagnosis of TSC. In addition, a definite diagnosis
of TSC can be made on the basis of the clinical
criterion of the presence of two major features
or the presence of one major feature with two or
more minor features (Table 1). A possible diag­
nosis of TSC requires the presence of one major
feature or two or more minor features.
Dermatologic Manifestations
Dermatologic manifestations are seen in nearly
100% of persons with TSC, and many are con­
sidered major features of the clinical diagnosis
(1,10). Hypomelanotic macules or ash-leaf spots
are the most common dermatologic manifes­
tations; they often develop at birth or during
infancy and may be the first clinical signs of TSC.
These manifestations appear as elliptic hypo­
pigmented macules and may become more ap­
preciable with age or under a Wood lamp.
Facial angiofibromas appear as pink to red
dome-shaped papules in the malar area (Fig 1).
They typically manifest during preschool years.
Fibrous cephalic plaques often occur unilaterally
on the forehead during early childhood and are
similar to angiofibromas at histologic analysis.
Ungual fibromas are less common and usually
manifest as smooth firm nodular lesions adjacent
to or underneath the nails in adolescents and
1994 November-December 2021
adults. Shagreen patches appear as large grayish-
green or light brown thick plaques with a bumpy
surface in the lumbosacral region; they manifest
during the 1st decade of life.
“Confetti” skin lesions typically appear as tiny
1–3-mm hypopigmented macules that may be
scattered throughout the body. Skin lesions tend
to increase in size and number through puberty
and then become stable over time. There is no
substantial risk of malignant transformation
of these skin lesions. However, if they rapidly
change or become symptomatic or disfiguring,
various therapies such as surgical excision, laser
therapy, and topical mTOR inhibitors may be
considered (4).
Ophthalmic Manifestations
Multiple retinal hamartomas, or Lisch nodules,
are considered a major feature in the diagnosis
of TSC. They occur in 30%–50% of affected
patients (1). These malformations rarely affect
vision and do not require a specific treatment.
Other ophthalmic manifestations include retinal
achromic patches, eyelid angiofibromas, non­
paralytic strabismus, and colobomas. Annual
ophthalmic evaluation is recommended for those
in whom ophthalmic manifestations have been
identified (4).
Central Nervous System
Manifestations
There are four classic central nervous system
findings associated with TSC: cortical and sub­
cortical tubers, cerebral white matter heterotopia,
subependymal nodules, and SEGAs (Figs 2–8).
Central nervous system manifestations account
for the major causes of morbidity and mortality
among persons with TSC, occurring in more than
80% of these individuals (9). Seizures are the
most common neurologic complication, occur­
ring in 75%–90% of patients with TSC. Mental
retardation occurs in approximately 50% of these
patients. Other neurobehavioral disorders such as
autism, attention deficit, hyperactivity, and sleep
disorders also may occur, although they are less
common (10).
Cortical and Subcortical Tubers
Cortical and subcortical tubers occur in 90% of
persons with TSC and are composed of enlarged
atypical and disorganized neuronal and glial ele­
ments with astrocytosis (1,11). They occur as a
result of disorganized cortical lamination and can
appear anywhere, from the cortex to white mat­
ter. Similar to white matter heterotopia, cortical
and subcortical tubers are regarded as corti­
cal dysplasias, which are a major feature in the
clinical diagnosis of TSC (1). Cortical tubers are
radiographics.rsna.org
Table 1: Major and Minor Clinical Features of
TSC
Major features
Hypomelanotic macules
Angiofibromas or fibrous cephalic plaque
Ungual fibromas
Shagreen patch
Multiple retinal hamartomas
Cortical dysplasias
Subependymal nodules
SEGA
Cardiac rhabdomyoma
LAM*
AML*
Minor features
“Confetti” skin lesions
Dental enamel pits
Intraoral fibromas
Retinal achromic patch
Multiple renal cysts
Nonrenal hamartomas
Note.—On the basis of the 2012 updated Interna­
tional TSC Consensus Group diagnostic criteria
(1), a definite diagnosis of TSC requires the pres­
ence of two major features or one major feature
with two or more minor features.
*When both LAM and AML are present, other
TSC features must be present for a definite diag­
nosis of TSC because sporadic LAM can often be
seen in combination with renal AML.
typically benign pathologic entities. However, the
extent of cerebral dysfunction, including intrac­
table epilepsy and mental retardation, may be
related to the burden from cortical tubers, espe­
cially when there is bilateral hemisphere involve­
ment (9,10,12). Cortical tubers may serve as the
epileptogenic focus and are generally resected in
cases of intractable epilepsy.
On CT images, tubers are hypoattenuating and
occasionally demonstrate calcification. At MRI,
tubers are hypointense on T1-weighted images and
hyperintense on T2-weighted and fluid-attenuated
inversion-recovery (FLAIR) images (Fig 2) (Table
2). When calcified, they demonstrate susceptibil­
ity artifacts (11,13). This MRI pattern is reversed
in infants owing to the relative absence of my­
elination. Central cystic degeneration may occur.
Cortical tubers that demonstrate heterogeneous
signal intensity—characterized by a hypointense
central region surrounded by a hyperintense rim—
on FLAIR MR images are associated with epilep­
tic seizures (21). Advanced imaging techniques
can aid in identification of epileptogenic tubers.
At diffusion-tensor imaging, epileptogenic tubers
RG • Volume 41 Number 7
Figure 1. Facial angiofibromas in a 23-year-old woman with
tuberous sclerosis. Medical photograph shows multiple tiny
dome-shaped papules in the malar region arranged in the
characteristic butterfly distribution.
Figure 2. Multiple cortical tubers in a 46-year-
old woman with tuberous sclerosis. Axial FLAIR
MR image shows multiple hyperintense lesions
(arrow) in the cortex, consistent with cortical
tubers.
have higher apparent diffusion coefficients and
lower fractional anisotropy (22). On fluorine 18–
fluorodeoxyglucose PET scans, they demonstrate
glucose hypometabolism (23).
If ictal discharges are detected, early epilepsy
treatment can be beneficial in children, regard­
less of the clinical manifestations (4). Medica­
tion therapies include those with vigabatran and
adrenocorticotropin hormone. In patients with
medically refractory epilepsy, neurosurgical in­
tervention can be considered (4). In this setting,
imaging may be particularly helpful, serving as a
road map for localizing the epileptogenic tubers.
White Matter Heterotopia
White matter heterotopia is commonly found
in patients with TSC, occurring in more than
80% of these individuals (11). Nodules, cysts,
foci of gliosis, and hypomyelination may be seen
along the path of migration from the ventricle
to the cerebral cortex. These entities may even
terminate in a subcortical tuber, given the similar
Wang et al 1995
migration aberration of white matter hetero­
topia and subcortical tubers. Like cortical tubers,
white matter heterotopia is considered a cortical
dysplasia, which is a major feature in the clinical
diagnosis of TSC (1). White matter heterotopia
is also similar to cortical tubers in that it also is
associated with intractable epilepsy and learning
difficulties.
White matter heterotopia may not be well vi­
sualized on CT images and is better appreciated
on MR images. At MRI, white matter heterotopia
may demonstrate T1 isointensity or hypointensity,
T2 hyperintensity, and rare enhancement (Fig 3)
(13). When white matter heterotopia is associated
with white matter cysts, it has low attenuation
on CT images and is isointense to cerebrospinal
fluid on MR images (11,24).
Subependymal Nodules
Subependymal nodules have a histologic com­
position that is similar to that of cortical tubers,
and they occur in more than 90% of individuals
with TSC (Figs 4–6) (13). This is a major fea­
ture in the clinical diagnosis of TSC (1). These
nodules tend to calcify with the affected per­
son’s age; therefore, CT is the preferred imaging
modality for identifying them in undiagnosed
patients. These benign growths occur along the
ependymal surface of the lateral ventricles. On
noncontrast CT images, subependymal nod­
ules appear as multiple small foci with dense
calcification (Fig 4). At MRI, they are iso- to
hyperintense on T1-weighted images, are iso- to
hyperintense on T2-weighted and FLAIR im­
ages, and demonstrate variable enhancement
(Fig 5) (13,25). When calcified, subependymal
nodules demonstrate susceptibility artifacts on
MR images (Fig 6).
Subependymal Giant Cell Astrocytomas
SEGAs are characteristic brain tumors in individ­
uals with TSC, occurring during late childhood
in 10%–15% of persons with this complex (Figs
7, 8) (1,13). These benign slow-growing tumors
are presumed to arise from subependymal nod­
ules and occur near the foramen of Monro (13).
They are a major feature in the clinical diagnosis
of TSC (1). Depending on their size and location,
SEGAs may cause obstructive hydrocephalus,
resulting in symptoms that include headaches,
vomiting, focal neurologic deficits, fatigue, and
increased seizure frequency.
At MRI, SEGAs may have variable signal
intensity and be iso- to hypointense compared
with the cortex on T1-weighted images and
heterogeneously iso- to hyperintense compared
with the cortex on T2-weighted images (25).
However, compared with subependymal nodules,
1996 November-December 2021 radiographics.rsna.org

Table 2: Imaging Features of Common TSC-related Manifestations

Common Commonly Used Imaging

Manifestations Modality or Modalities Imaging Features
Cortical and sub­ CT, MRI T2-hyperintense and T1-hypointense cortical and subcortical
cortical tubers nodules with or without calcification and cystic degeneration
White matter MRI Nodules, cysts, and areas of gliosis, extending from ventricle to
heterotopia cerebral cortex, that are T1 isointense or hypointense and T2
hyperintense
Subependymal CT, MRI Nodules that are T1 isointense to hyperintense and T2 iso­intense
nodules to hyperintense along the ependymal surface of lateral ven­
tricles with or without dense calcification
SEGAs CT, MRI Similar to subependymal nodules but larger and with more avid
enhancement, large nodules are often near the foramen of
Monro, may cause obstructive hydrocephalus
Cardiac rhabdo­ US, MRI Well-defined hyperechoic mass on the ventricular septum, T1
myoma isointense to myocardium and T2 hyperintense
LAM High-resolution CT Diffuse, thin-walled, well-defined bilateral pulmonary cysts that
vary in size and are devoid of internal structures
MMPH High-resolution CT Diffuse tiny pulmonary nodules in random distribution
Renal AML US, CT, MRI Lipid-rich: hyperechoic when small and heterogeneous when
large, solid mass with variable enhancement and regions of fat,
signal drop at fat-suppressed MRI and india ink artifact at the
tumor-renal interface (indicative of macroscopic fat)
Lipid-poor: T1 and T2 hypointense, may not have signal drop
at fat-suppressed MRI, may not have india ink artifact at the
tumor-renal interface
Renal cysts US, CT, MRI Simple-appearing thin-walled cysts
RCC US, CT, MRI Heterogeneous solid renal mass without macroscopic fat, vari­
able T2 signal intensity and enhancement characteristics
Non-AML MRI T2 hyperintense compared with muscle, with or without central
PEComa necrosis; may demonstrate hematogenous metastases to lung,
liver, and bone; large tumor vessels
Sources.—References 13–20.

SEGAs are larger (>1 cm), calcify incompletely, Cardiac Manifestations

and demonstrate more avid enhancement (Fig
7) (11). New symptoms, hydrocephalus, and en­
largement at follow-up imaging should alert the
clinician to development of SEGAs (Fig 8). MR
spectroscopy may be used to differentiate SEGAs
from subependymal nodules; SEGAs have high
choline-to-creatine ratios and low N-acetylaspar­
tate–to-creatine ratios (26).
Generally, brain MRI surveillance is recom­
mended every 1–3 years until the patient is age
25 years. At age 25 years, the need for further
surveillance depends on the presence or absence
of SEGAs. Patients without SEGAs do not
require continued surveillance, while those with
SEGAs—even if they are asymptomatic—need
lifelong surveillance owing to the potential for
growth and development of hydrocephalus (4).
When a patient is symptomatic, surgical resection
is recommended. Furthermore, mTOR pathway
inhibitors may be used to decrease the size of
these tumors (27).
Cardiac Rhabdomyoma
Cardiac rhabdomyomas are considered a major
feature of TSC. They manifest in up to 80% of
TSC cases and are rarely seen in persons who
do not have this disease (1,28). Therefore, TSC
should be suspected if cardiac rhabdomyomas are
identified (14). The majority (90%) of persons
with TSC are found to have multiple rhabdo­
myomas after they present (14,15). At gross
pathologic examination, cardiac rhabdomyomas
are well-circumscribed nonencapsulated masses
with diameters ranging from 2 to 20 mm (15,28).
These benign tumors are characterized by irregu­
lar myocyte architecture, including “spider”cells,
which are so named because of their unique
cytoplasmic extensions (14,15).
Cardiac rhabdomyomas usually manifest at
20–30 weeks gestation and are often detected
on fetal US images, representing the first radio­
logic indication of TSC in about 60% of patients
RG • Volume 41 Number 7
Figure 4. Subependymal nodules in a 26-year-old woman with tuberous
sclerosis. Axial noncontrast CT image of the brain shows multiple calcified
subependymal nodules (arrows). Pneumocephalus secondary to prior brain
surgery also is seen.
(15,28). On US images, these tumors appear as
well-defined, hyperechoic, homogeneous masses
and are typically embedded in the ventricles (Fig
Wang et al 1997
Figure 3. White matter hetero­
topia in a 23-year-old woman with
tuberous sclerosis. (A) Axial FLAIR
MR image shows radial linear white
matter lesions (arrow) extending
from the cortex to the ventricle.
(B) Axial T2-weighted MR image
shows linear hyperintense white
matter lesions (arrow) extending
from the cortex. These lesions may
represent areas of demyelination,
dysmyelination, or hypomyelin-
ation. (C) Axial noncontrast T1-
weighted MR image shows iso­
intense linear white matter lesions
(arrow) extending from the cortex.
(D) Axial contrast-enhanced T1-
weighted MR image shows mild
enhancement (arrow) within the
linear white matter lesions.
9) (13). Although rhabdomyomas are gener­
ally asymptomatic, arrhythmia, hemodynamic
compromise, or nonimmune fetal hydrops may
indicate their presence and are predictors of poor
neonatal outcome (15,29,30).
If the diagnosis is not made antenatally, echo­
cardiography usually is required and will reveal
one or more small tumors in the ventricular free
wall or ventricular septum. Echocardiography is
also useful for assessing cardiac inflow and outflow
complications caused by these tumors (13,15).
Atypical rhabdomyomas, such as those located
in the atria or that appear as large solitary neo­
plasms, may prove challenging to diagnose with
echocardiography alone (15). MRI is a useful
alternative when US findings are inconclusive.
1998 November-December 2021 radiographics.rsna.org

Figure 5. Subependymal nod-

ules in a 40-year-old woman with
tuberous sclerosis. (A) Axial non-
contrast T1-weighted MR image
shows multiple subependymal
nodules (arrow) with intermediate
signal intensity. (B) Axial contrast-
enhanced T1-weighted MR image
shows enhancement of the sub­
ependymal nodules (arrow).

Figure 6. Subependymal nodules in a 33-year-old woman with tuberous

sclerosis. Axial T2∗-weighted MR image shows hypointense calcified sub­
ependymal nodules (arrow).

On MR images, cardiac rhabdomyoma mani­

fests as a homogeneous mass that is mildly T2
hyperintense relative to the surrounding myo­
cardium and T1 isointense. These tumors are
T1 hypointense to the myocardium on first-pass
perfusion MR images and isointense on delayed
intravenous gadolinium–enhanced MR images
(13,28,31).
Spontaneous regression occurs with 70%
of cardiac rhabdomyomas by the time the af­
fected person is aged 4 years (14). However, in
a minority of cases, cardiac rhabdomyomas can
result in serious complications such as heart
failure, valvular dysfunction, irregular out­
flow, and fatal arrhythmia (13,15). In addition,
transient enlargement of these tumors during
puberty also has been reported (32). For these 50% and positive predictive value of 100% for
reasons, follow-up echocardiography to docu­ TSC. Similarly, Adriaensen et al (39) reported
ment tumor resolution is recommended (28). myocardial fat foci in 64% of patients with TSC.
Typically, asymptomatic patients with cardiac On echocardiograms, these foci are hyperechoic
rhabdomyomas undergo active surveillance (29). without visible vascularity. On CT images, they
Surgical intervention is indicated only if the appear as small well-circumscribed regions of
affected patient develops any of the aforemen­ fat attenuation that typically arise from the left
tioned potentially life-threatening complications ventricular wall or interventricular septum (Fig
(14). Therapy with mTOR inhibitors may be an 10) (28). At MRI, these foci demonstrate fat
option for treating large tumors detected during signal intensity and are easily identified with fat-
the neonatal period (33–36). suppressed sequences.

Myocardial Fat Foci Pulmonary Manifestations

Multiple case reports of myocardial fat foci
in patients with TSC have been published
(16,37–40). Although not an official criterion
for TSC, these foci have shown specificity for
TSC. Tresoldi et al (40) demonstrated that the
presence of myocardial fat foci has sensitivity of
Lymphangioleiomyomatosis
LAM is the most common pulmonary manifesta­
tion of TSC, occurring in 26%–57% of affected
patients (Figs 11, 12) (41). LAM occurs as a result
of proliferation of smooth muscle cells throughout
RG • Volume 41 Number 7 Wang et al 1999

Figure 7. SEGA in a 26-year-old

woman with tuberous sclerosis.
(A) Axial FLAIR MR image shows
a large heterogeneously hyper-
intense SEGA (arrow) at the level
of the foramen of Monro. Associ-
ated hydrocephalus also is seen.
(B) Coronal contrast-enhanced
T1-weighted MR image shows avid
enhancement within the SEGA (ar-
row). The tumor is also encroach-
ing on the frontal horns.

Figure 8. SEGA in a 32-year-old man who has tuberous sclerosis with acute headache and vomiting. (A) Axial T2-weighted MR
image shows a large SEGA (arrow) near the foramen of Monro. (B) Axial T2-weighted MR image shows marked hydrocephalus
(arrow) resulting from the SEGA. (C) Axial contrast-enhanced T1-weighted MR image shows avid enhancement in the SEGA
(arrow).

Figure 9. Cardiac rhabdomyomas in a 36-weeks pregnant woman with a known history of tuberous sclerosis. Modified apical
four-chamber–view fetal echocardiograms show multiple solid hyperechoic lesions (arrows) in the right and left ventricles (V). These
lesions are diagnostic of cardiac rhabdomyomas. IVS = interventricular septum.
2000 November-December 2021 radiographics.rsna.org

Figure 10. Myocardial

fat and pulmonary LAM
in a 62-year-old woman
with tuberous sclerosis.
(A) Sagittal noncon-
trast CT image of the
chest shows myocardial
fat (arrows). (B) Sagit-
tal noncontrast CT im-
age of the chest shows
multiple small, thin-
walled pulmonary cysts
(arrows).

the peribronchial, perivascular, and perilymphatic

regions of the lung (41). This entity belongs to the
PEComa family, which also includes AML (42).
It should be noted that LAM may also occur spo­
radically and needs to be distinguished from TSC-
associated LAM. Sporadic LAM occurs almost
exclusively in women; in contrast, TSC-associated
LAM may occur in men in 10%–38% of cases
(43–46). Sporadic LAM is also associated with
renal AMLs (30%), but it has no association with
polycystic kidney disease. In comparison, TSC-
associated LAM has a strong association with both
renal AMLs (80%) and polycystic kidney disease
(43–46). In addition, sporadic LAM is associated
with more extensive pulmonary involvement and
a higher frequency of lymphatic complications
Figure 11. Pulmonary LAM in a 26-year-old woman
(including chylothorax) compared with TSC-­ with tuberous sclerosis. Coronal intravenous contrast–
associated LAM (43–46). enhanced CT image of the chest shows diffuse small,
Lung involvement has been shown to increase thin-walled pulmonary cysts in both lungs.
with age, with up to 80% of females with TSC
affected by age 40 years (47). While pulmonary
cysts may be seen during childhood, symptoms
including progressive dyspnea, cough, pneumo­
thorax, and chylothorax usually manifest during
adulthood. LAM-related complications include
recurrent pneumothoraces (Fig 12) and chylous
pleural effusions or ascites. When both LAM
and AML are present, other TSC features must
be present for a definite diagnosis of TSC, as
sporadic LAM can often be seen in combination
with renal AMLs (1).
On chest CT or high-resolution CT images,
LAM exhibits numerous thin-walled, fairly Figure 12. Pulmonary LAM and pneumothorax in a
homogeneous pulmonary cysts in all lung zones 20-year-old woman with tuberous sclerosis. Axial CT
and is devoid of internal structures (Figs 11, 12) image of the chest shows small, thin-walled pulmo-
nary cysts (straight arrows) and right pneumothorax
(13,17,48). The predominant cyst size correlates (curved arrow).
with the disease extent, with larger cysts associ­
ated with more severe and extensive disease (48).
Measurements of serum levels of vascular status and disease progression. A VEGF-D level
endothelial growth factor type D (VEGF-D) may higher than 800 pg/mL in patients with cystic
be helpful in establishing the patient’s baseline changes at CT is diagnostically specific for LAM
RG • Volume 41 Number 7
Figure 13. Pulmonary MMPH in a 41-year-old man with tuberous sclerosis. (A) Coronal lung-win-
dow CT image of the chest shows tiny scattered pulmonary nodules (arrows) randomly distributed
in both lungs. (B) Axial CT image of the chest shows a faint ground-glass nodule (long arrow) in the
right lower lobe. Small pulmonary cysts (short arrows) related to LAM also are seen.
(49). However, normal VEGF-D levels do not
exclude a diagnosis of LAM. Surveillance with
high-resolution CT should be performed every
5–10 years in asymptomatic patients who do not
have LAM at baseline high-resolution CT.
Once cysts are detected, the patient should
undergo high-resolution CT surveillance every
2–3 years or sooner, along with annual pulmo­
nary function testing and the 6-minute walk test
(4). Patients with mildly impaired lung function
should be monitored clinically, while those with
moderate-to-severe lung function impairment
should be treated with mTOR inhibitor therapy.
Patients with severe lung disease refractory to
mTOR inhibitors should be considered for lung
transplantation (4).
Multifocal Micronodular Pneumocyte
Hyperplasia
MMPH is another TSC-related pulmonary
manifestation. This hyperplasia represents benign
hamartomatous proliferation of type II pneumo­
cytes manifesting as multiple tiny pulmonary nod­
ules. Histologically, the nodules are composed of
thickened fibrotic alveolar septa lined by pleomor­
phic type II pneumocytes (50). This finding may
occur in up to 43% of TSC cases and appears to
be more common than previously recognized (18).
MMPH rarely manifests without TSC or LAM.
Clinically, MMPH is usually asymptomatic
and not progressive. If symptoms are present,
dyspnea, cough, and mild to moderate hypoxemia
may be seen. On high-resolution CT images,
MMPH manifests as tiny diffusely scattered
1–10-mm pulmonary nodules arranged in a
random distribution (17). Although solid nodules
are more common, MMPH may also appear as
nodular ground-glass opacities (Fig 13) (51).
These nodules have a slight predilection for the
lung periphery and upper lobes (18).
Wang et al 2001
Abdominal Manifestations
Renal AMLs
Similar to LAM, AMLs are mesenchymal tumors
categorized under the PEComa family of neo­
plasms (28,42). These tumors originate from
clonal proliferation of epithelioid cells located
around blood vessels. AMLs may be found in
multiple organs, most notably the kidneys, and
the presence of two or more of these tumors is
considered a major feature of TSC (1,28). Renal
AMLs can be identified in 55%–75% of patients
with TSC (Figs 14–18) (1). They are often dis­
covered incidentally owing to their asymptomatic
nature; however, they can manifest with abdomi­
nal pain, hematuria, anemia, hypertension, and/or
retroperitoneal hemorrhage (Fig 14). Renal
AMLs can multiply and grow during puberty,
suggesting an estrogenic influence (14,52).
There are two histologic subtypes of AML:
classic and epithelioid. At gross pathologic ex­
amination, classic AML appears as a well-defined
expansile mass in the renal cortex or medulla.
Tortuous vasculature, clear to eosinophilic cells,
and spindle cells are visible at microscopy. Epi­
thelioid AMLs occur more frequently in patients
with TSC (27%) than in the general population
(7%) (Fig 15) (53). Malignant transformation of
epithelioid AMLs can occur and may be sus­
pected in the presence of rapid growth or ne­
crosis. In contrast, classic AMLs tend to remain
benign (52).
Renal AMLs are classified as lipid-rich, lipid-
poor, and lipid-invisible subtypes on the basis of
the amount of fat demonstrated on CT or MR
images (Figs 16, 17) (54). This fat can lead to
varying imaging appearances that often result
in misinterpretation. To our knowledge, there is
no corresponding histopathologic fat quantifica­
tion threshold for each AML subtype. However,
2002 November-December 2021
Figure 14. Renal AML in a
25-year-old woman with tuberous
sclerosis. (A) Coronal CT image
of the abdomen shows multiple
left renal AMLs (arrows). The pa-
tient had previously undergone
right nephrectomy and was lost to
follow-up for 2 years. (B) Coronal
CT image of the abdomen shows
extensive left renal and retroperito-
neal hemorrhage (arrow) second-
ary to rupture of one of the left
renal AMLs.
AMLs without visible fat have been shown to
have fewer than 25% adipocytes per high-power
field, while AMLs with visible fat have more
than 25% adipocytes per high-power field (55).
Ninety-five percent of renal AMLs are lipid rich
and easily diagnosed with imaging. On US im­
ages, small AMLs appear homogeneous and hy­
perechoic relative to the renal parenchyma, while
larger AMLs are more heterogeneous owing to
varying compositions of vasculature and smooth
muscle. Posterior acoustic shadowing may be
present in 30% of AMLs. Nevertheless, distin­
guishing AML with US alone is difficult (13,56).
The hallmark finding of lipid-rich AML is
the presence of intratumoral fat with an attenu­
ation of −10 HU or lower on noncontrast CT
images (54). These tumors demonstrate variable
enhancement. It should be noted that RCC may
rarely demonstrate a small amount of intra­
tumoral fat, and this is a potential cause of di­
agnostic dilemmas. The presence of calcification
within a fat-containing renal mass should alert
the clinician to the diagnosis of RCC. In contrast,
calcification is extremely rare in AML (54).
A small subset of renal AMLs (5%) may not
demonstrate intratumoral fat on CT images
(lipid-poor or lipid-invisible AMLs), and distin­
guishing these from RCC can be a major diag­
nostic challenge (14,52). Lipid-poor and lipid-
invisible AMLs are hyperattenuating compared
with the surrounding parenchyma on noncon­
trast CT images and demonstrate moderate to
avid enhancement on multiphasic CT images.
The presence of an angular interface is another
feature that may suggest AML (57). However,
distinguishing lipid-poor or lipid-invisible AML
from RCC on the basis of CT features alone
remains extremely challenging, and biopsy is gen­
erally required to confirm the diagnosis (54,58).
radiographics.rsna.org
MRI may aid in discriminating AML sub­
types from RCC. Lipid-rich AML containing
macroscopic fat will appear T1 hyperintense
and demonstrate signal loss with fat saturation
on MR images. In addition, india ink artifact
will be visible at the fat-water interface between
lipid-rich AML and the renal parenchyma on
chemical shift MR images (Fig 17) (13,28).
AMLs may also contain microscopic fat, which
can demonstrate signal dropout on opposed-
phase MR images. It should be noted that while
the presence of macroscopic fat is pathogno­
monic of AMLs, the presence of microscopic fat
is not diagnostic of AMLs.
Lipid-poor or lipid-invisible AMLs are hypo­
intense relative to the renal parenchyma on
T1- and T2-weighted MR images and may not
demonstrate signal loss at fat-saturated or out-
of-phase MRI (54). Differentiating lipid-poor or
lipid-invisible AML from RCC—which gener­
ally manifests as a solid renal mass with variable
T2 signal intensity and enhancement character­
istics and absence of macroscopic fat—can be
challenging. The T2 hypointensity of AML is a
useful feature, as it can help differentiate AML
from the clear cell RCC subtype, which usually
demonstrates heterogeneously high T2 signal
intensity (28,54). Although papillary RCC is
also T2 hypointense, its enhancement charac­
teristics are significantly different from those of
AML. Papillary RCC is typically hypovascular,
whereas AML tends to demonstrate moderate
to avid enhancement. When the diagnosis is still
unclear at imaging, percutaneous biopsy should
be performed.
Renal AMLs represent the second most
frequent cause of morbidity among patients
with TSC owing to the risk of spontaneous
hemorrhage and rupture (Fig 14). Such com­
RG • Volume 41 Number 7 Wang et al 2003

Figure 15. Epithelioid renal

AML in a 33-year-old woman
with tuberous sclerosis. (A) Axial
T2-weighted fat-suppressed MR
image shows a heterogeneous
hypointense mass (arrow) in the
right kidney. (B) Axial contrast-
enhanced T1-weighted MR im-
age shows avid enhancement,
just slightly lower than that of the
adjacent renal cortex, in the right
renal mass (arrow). Biopsy results
confirmed epithelioid renal AML.

Figure 16. Bilateral renal AMLs in a 26-year-old woman with tuberous

sclerosis. Coronal CT image shows multiple bilateral macroscopic fat-
containing renal AMLs (arrows). The right lower pole mass demonstrates
a draining vessel that branches from the renal cortex. Note that the right
upper pole and lower pole renal masses demonstrate an angular interface
with the renal parenchyma.

Renal cysts are usually multiple and bilateral.

plications occur increasingly with AMLs that
are larger than 4 cm or those that are associated
with aneurysms larger than 5 mm. If either of
these criteria is met, embolization or nephron-
sparing surgery is highly recommended (Fig
18). Tumors that do not fulfill this criterion
are followed up conservatively or treated with
mTOR inhibitors, elective embolization, ablative
therapies, or nephron-sparing surgery (10,13).
Lifelong follow-up with abdominal MRI every
1–3 years is recommended (52).
Renal Cysts
Renal cysts are the second most prevalent renal
feature of TSC, occurring in 17%–47% of pediat­
ric patients with TSC (28). Because of their low
specificity, multiple renal cysts are considered a
minor feature of TSC. TSC-related renal cysts
can appear with varying severity, from micro­
scopic disease to a serious polycystic variation.
The polycystic variation occurs in about 2%–3%
of patients with TSC and results from contiguous
mutations of TSC2 and polycystic kidney disease
type 1 (PKD1) genes, which are located close to
each other on chromosome 16p13.3 (1,13).
They tend to multiply and grow with time, from
a few millimeters to several centimeters in diam­
eter. Similar to polycystic kidney disease, renal
cysts are anechoic and multiple at US. On MR
images, they have high fluid signal intensity and
no internal enhancement. Occasional internal
hemorrhage may demonstrate T2 hypointensity
and T1 hyperintensity (28). Complications are
usually associated with the polycystic variation,
which can lead to hypertension and renal failure
during early adulthood (13). Renal cystic dis­
ease should be monitored every 1–3 years with
abdominal MRI (4).
Renal Cell Carcinomas
RCC occurs in only 2%–3% of persons with
TSC, similar to its prevalence in the general
population (Fig 19) (13). However, unlike
sporadic RCC, TSC-related RCC occurs in
comparatively young individuals—in whom the
median age at diagnosis is 28 years—and tends
to be less aggressive (28). TSC-related RCC
can be categorized into three major histologic
subtypes: papillary, chromophobe, and clear cell.
These subtypes tend to exhibit different imag­
ing patterns owing to their varying histologic
components.
Papillary RCCs enhance gradually, while chro­
mophobe carcinomas demonstrate weak homo­
geneous early enhancement and washout. Con­
versely, clear cell RCCs are highly vascular and
thus demonstrate stronger early enhancement
followed by early washout (13,52). Although dif­
ferentiation of RCC from AML has been dis­
cussed, in cases in which the distinction between
2004 November-December 2021 radiographics.rsna.org

Figure 17. Renal AMLs in a 21-year-old woman with tuberous sclerosis. (A) Longitudinal US
image of the left kidney shows multiple hyperechoic masses (arrows). (B) Axial T1-weighted
in-phase MR image of the abdomen shows multiple hyperintense masses (arrows) in the left
kidney. (C) Axial T1-weighted out-of-phase MR image of the abdomen shows multiple masses
in the left kidney. Note the india ink artifact (arrows) at the water-mass (fat) interface in the left
renal masses, indicating the presence of macroscopic fat. (D) Axial CT image of the abdomen
shows the macroscopic fat in the left renal masses (arrows).

Figure 18. Renal AML in a 33-year-old woman with tuberous sclerosis. Pre-embolization (A)
and postembolization (B) angiograms show a large left renal AML. (A) Pre-embolization image
shows extensive vascularity and numerous small tortuous aneurysms (arrows) in the left renal
AML. Two tiny vessels supplying the solid left renal AML were embolized with 2 mL of absolute
ethanol. (B) Postembolization angiogram shows that the blood flow to the AML has been cut
off, confirming successful embolization.
RG • Volume 41 Number 7
Figure 19. RCC in a 43-year-old man with tuberous sclerosis. (A) Axial T1-weighted MR image shows a macroscopic fat–containing
AML (arrow). (B) Axial T2-weighted MR image shows a heterogeneous mass in the right kidney, with central cystic and/or necrotic
components (arrow). (C) Axial contrast-enhanced T1-weighted fat-suppressed MR image shows heterogeneous enhancement in the
right renal mass. Central cystic nonenhancing areas (arrow) are again seen.
Figure 20. Fat-containing hepatic AMLs in a 36-year-
old woman with tuberous sclerosis. Axial abdominal CT
image shows multiple small fat-containing lesions (small
arrows) in the liver, diagnostic of hepatic AMLs. Left re-
nal AMLs (large arrows) also are seen.
AML and RCC cannot be made with certainty,
image-guided biopsy should be performed. The
mainstay of therapy is surgical resection.
Hepatic AMLs
Hepatic AML is a relatively common benign
feature of TSC, occurring in 16%–24% of TSC
cases (13). These neoplasms are frequently mul­
tiple and may be seen in patients with coexisting
renal AMLs (28). Hepatic AMLs are gener­
ally asymptomatic, but they may manifest with
abdominal pain or an abdominal mass. At gross
pathologic examination, they are characterized
by a heterogeneous mixture of smooth muscle,
adipose tissue, and vascular tissue (59). Because
of their varying compositions, hepatic AMLs have
heterogeneous imaging appearances (Figs 20–22)
(60). On contrast-enhanced US, CT, and MR
images, the majority of these neoplasms demon­
strate hypervascularity during the arterial phase
and sustained enhancement during subsequent
phases (60,61).
Isoenhancement is another common appear­
ance of hepatic AMLs, and up to 25% of these le­
Wang et al 2005
sions may demonstrate washout. On MR images,
they exhibit variable T1 and T2 signal intensity,
depending on their fat content. Similar to renal
AMLs, hepatic AMLs generally demonstrate sig­
nal loss on fat-suppressed MR images, reflecting
macroscopic fat, and india ink artifact on op­
posed-phase MR images, also reflecting macro­
scopic fat. Fat in combination with prominent
vessels is a specific imaging feature of hepatic
AMLs (60). Although the risk of spontaneous
rupture and hemorrhage is low, resection should
be considered for tumors that are symptomatic or
larger than 4 cm. Otherwise, small hepatic AMLs
may be monitored (13,62).
Splenic Hamartomas
Splenic hamartomas are rarely seen in persons
with TSC. Most (80%) of these malformations
are asymptomatic and discovered incidentally
(63). Histologically, the majority of splenic ham­
artomas are composed of a mixture of red and
white splenic pulp, resulting in hypervascularity
(13,64). On US images, splenic hamartomas are
typically solid masses that are hyperechoic to
the surrounding splenic parenchyma and have
increased color Doppler flow. Cystic changes and
calcification are commonly observed (13,63).
On CT images, splenic hamartomas are often
iso­attenuating to the background spleen; thus,
splenic contour deformation serves as a useful
finding (13,65,66). Small splenic hamartomas are
usually T1 and T2 isointense to the background
spleen at MRI. When these malformations are
large, they usually demonstrate mild T2 hyper­
intensity and T1 hypointensity with internal scat­
tered T1 and T2 hypointensity on MR images, re­
flecting fibrous tissue (13,64). They demonstrate
diffuse enhancement on early contrast-enhanced
MR images and become more homogeneous
with delayed sequences (64). Given the rarity
of splenic hamartomas, there are no published
guidelines for their treatment or follow-up, to our
knowledge.
2006 November-December 2021
Other Manifestations
PEComas are rare mesenchymal neoplasms with
variable tumor biologic features and oncologic
outcomes (67). These tumors are composed of
perivascular epithelioid or spindle cells that ex­
press smooth muscle and melanocytic markers,
such as HMB-45 actin, and they are arranged
around blood vessels (42,68). PEComas demon­
strate alterations in the TSC genes and therefore
result in common TSC manifestations such as
AML and LAM. However, multiple studies
have demonstrated uncommon TSC-related
PEComas other than the usual AML and LAM
manifestations, such as PEComas in the uterus
(19,69,70). These tumors are generally of low
grade and are associated with a good prognosis
(28). However, a small group of PEComas may
demonstrate malignant behavior. At histologic
analysis, potentially malignant PEComas dem­
onstrate two or more of the following features:
large size (>5 cm), infiltrative growth, high
nuclear grade and hypercellularity, one or more
mitoses per 50 high-power fields, necrosis, and
vascular invasion (68). On MR images, non-
AML PEComas demonstrate avid enhancement
and T2 hyperintensity compared with muscle
(Fig 23). With growth, central necrosis may
develop. Some of these tumors may demonstrate
malignant behavior with hematogenous spread
to the lung, liver, and bone (28). Given that
PEComas have a genetic alteration similar to
that of TSC, they potentially can be treated with
mTOR pathway inhibitors (68).
The reported osseous findings of TSC in­
clude sclerotic lesions, bone cysts, and periosteal
new bone formation along the metatarsal and
meta­carpal bones (71). Sclerotic lesions can be
identified in the ribs, in posterior elements of
the vertebrae, and along the iliac side of sacro­
iliac joints (Fig 24) (11). However, these osse­
ous manifestations are nonspecific findings and
thus not included in the diagnostic criteria for
TSC (1).
Vascular anomalies, including vascular dys­
plasias and aneurysms, have been reported with
TSC. Aside from the intratumoral aneurysms
associated with AML, TSC-related aneurysms
may be seen in other vessels, including the aorta,
cerebral arteries, and pulmonary arteries; how­
ever, these are rare (72). It is hypothesized that a
development defect of the arterial wall or vascu­
lar hamartoma that disrupts the vasa vasorum
may contribute to the pathogenesis of TSC-
related aneurysms, although the true pathogen­
esis remains unclear (72). Vascular occlusion is
extremely uncommon with TSC, although cases
involving the aorta, renal arteries, and mesenteric
arteries have been reported (73).
radiographics.rsna.org
Figure 21. Hepatic epithelioid AML in a 47-year-old
man with tuberous sclerosis. Coronal abdominal CT
image shows multiple large heterogeneous masses (ar-
rows) in the liver. No evidence of macroscopic fat is
seen. Biopsy findings confirmed the diagnosis of hepatic
epithelioid AML. Similar to renal AMLs, hepatic AMLs
may have minimal or no macroscopic fat, leading to di-
agnostic difficulties.
Management and Surveillance
A multidisciplinary approach with regular follow-
up from childhood to adulthood is mandatory
for management of TSC. Because of its multisys­
tem involvement with varying severity, a holistic
management approach is essential to minimizing
patient morbidity and mortality. In addition, ge­
netic counseling should be conducted when TSC
is suspected (4).
In patients who have newly diagnosed TSC
or are suspected of having TSC, comprehensive
clinical and imaging assessment is recommended
to establish the baseline status (4). Baseline brain
MRI, electroencephalography, and assessment
for TSC-associated neuropsychiatric disorders
should be performed. Abdominal MRI to evalu­
ate for hamartomas, as well as renal function
tests, also may be performed.
High-resolution CT and pulmonary function
tests should be performed to establish the pres­
ence of LAM. Patients should undergo counsel­
ing regarding smoking and estrogen use, which
can exacerbate the effects of LAM. Clinical
examination for possible skin, oral, and oph­
thalmic abnormalities is recommended. Cardiac
rhabdomyoma should be evaluated with baseline
echocardiography and electrocardiography.
For patients who have already received a diag­
nosis of TSC, continued surveillance is essential
to monitor disease progression and/or diagnose
RG • Volume 41 Number 7
Figure 22. Hepatic AML in a 66-year-old man with tuberous sclerosis. Axial arterial phase (A) and portal venous phase (B)
CT images show an avidly enhancing mass (arrow) in the right hepatic lobe. Biopsy results confirmed the diagnosis of
hepatic AML.
Figure 23. Pelvic PEComa in a 27-year-old woman with tu-
berous sclerosis. Coronal T2-weighted fat-suppressed MR im-
age of the pelvis shows an intermediate- to high-signal-inten-
sity heterogeneous mass (arrow) in the pelvis. Biopsy results
confirmed the diagnosis of PEComa.
new abnormalities (Table 3). With increasing
patient age, the culmination of multiple TSC-
related conditions in various organ systems may
lead to more complications in adulthood than in
childhood. Genetic counseling should be offered
when patients reach reproductive age. Suggested
managements for each organ system manifesta­
tion are summarized in Table 4.
Conclusion
TSC is an autosomal dominant neurocutane­
ous syndrome caused by mutations in the TSC1
or TSC2 tumor-suppressor gene. Patients with
TSC are at risk of developing numerous benign
hamartomatous tumors in various organ sys­
Wang et al 2007
Figure 24. Sclerotic bone lesions in a 34-year-
old man with tuberous sclerosis. Coronal bone-
window CT image of the thorax and abdomen
shows multiple scattered sclerotic lesions (short
arrows) in the vertebrae and pelvis. Macroscopic
fat–containing bilateral renal AMLs (large arrow)
also are seen.
tems. While some TSC-related manifestations
such as dermatologic and ophthalmic conditions
usually remain asymptomatic, other manifes­
tations—including cortical and subcortical
tubers, white matter heterotopia, subependymal
nodules, SEGAs, renal AMLs, RCCs, LAM,
and nonrenal PEComas—may be associated
with substantial patient morbidity and mortal­
ity. Radiologists have an essential role in early
diagnosis and lifelong follow-up of patients with
these conditions.
2008 November-December 2021 radiographics.rsna.org

Table 3: TSC Surveillance Recommendations

Organ System(s) Surveillance Recommendations*

Genetics Genetic testing and family counseling, particularly for patients of reproductive age or those
considering having children
Skin and dental Annual dermatologic assessment
Clinical dental examination every 6 months and panoramic radiography by age 7 years
Eye Annual ophthalmologic examination in those with previously identified eye lesions or vision
symptoms
Brain MRI of brain every 1–3 years, MRI of brain more frequently if there are large or growing
SEGAs or there is asymptomatic SEGA causing ventricular enlargement
Annual screening for possible TSC-associated neuropsychiatric disorders
Routine electroencephalography in those with known or suspected seizure activity
Heart Echocardiography every 1–3 years in asymptomatic patients until regression of cardiac rhab­
domyomas is documented; echocardiography more frequently in symptomatic patients
Electrocardiography every 3–5 years in asymptomatic patients to monitor for conduction
defects
Lung Annual evaluation for possible exertional dyspnea, pulmonary function testing
Counseling regarding risk factors such as smoking, estrogen use, and pregnancy
Annual high-resolution CT if LAM is depicted at baseline high-resolution CT; if patient’s
condition is stable, interval can be reduced to every 2–3 years
High-resolution CT every 5–10 years in asymptomatic patients with no LAM at baseline
high-resolution CT
Kidney Lifelong abdominal MRI every 1–3 years, annual renal function testing
Sources.—References 1 and 4.
*Recommendations from the 2012 International Tuberous Sclerosis Complex Consensus Group (4).

Table 4: TSC Management Recommendations

Manifestation Type Management Recommendations*

Skin Symptomatic: surgery, laser therapy, or topical mTOR inhibitors
Ophthalmic Symptomatic: photodynamic therapy or vitrectomy
Seizures First line: vigabatrin
Second line: adrenocorticotropic hormone and other anticonvulsant agents
Refractory: surgery for epilepsy
SEGA Growing lesion: mTOR inhibitors
Acutely symptomatic: surgical resection and/or cerebrospinal fluid shunt
Refractory: surgical resection
Cardiac rhabdo­ Asymptomatic: follow-up, as these neoplasms regress with age
myoma Symptomatic: mTOR inhibitors and/or surgery
LAM Moderate-to-severe lung disease: mTOR inhibitors
Severe lung disease: lung transplant
Renal AML Acute hemorrhage: embolization and steroids; nephron-sparing approach is recommended
Growing, asymptomatic, >3 cm:
First line: mTOR inhibitors
Second line: elective embolization or nephron-sparing surgery
Sources.—References 1 and 4.
*Recommendations from the 2012 International Tuberous Sclerosis Complex Consensus Group (4).

Acknowledgment.—We thank Kelly Kage for preparing some
of the images included in this article.
Disclosures of Conflicts of Interest.—S.B. Activities related
to the present article: member of RSNA Board of Directors
(not involved in the handling of this article). Activities not
related to the present article: disclosed no relevant relation­
ships. Other activities: disclosed no relevant relationships.
P.J.P. Activities related to the present article: disclosed no rel­
evant relationships. Activities not related to the present article:
paid consultant for Bracco and Zebra, payment for expert
testimony from National Institutes of Health, owns stock or
stock options in Shine Medical Technologies and Elucent.
Other activities: disclosed no relevant relationships. M.G.L.
Activities related to the present article: disclosed no relevant
relationships. Activities not related to the present article: insti­
tutional grants or grants pending from Philips Healthcare
and Ethicon. Other activities: disclosed no relevant relation­
RG • Volume 41 Number 7
ships. V.S.K. Activities related to the present article: editorial
board member of RadioGraphics (not involved in the han­
dling of this article). Activities not related to the present article:
disclosed no relevant relationships. Other activities: disclosed
no relevant relationships.
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