4/7/2015
Disclosures
Neonatal
Tumors
Shahab Abdessalam, MD
April 10, 2015
New Frontiers in Neonatal Care Conference
Objectives
Consultant/
Speakers bureaus
No Disclosures
Research funding
No Disclosures
Stock
ownership/Corporate
boards-employment
No Disclosures
Off-label uses
No Disclosures
Introduction
• Discuss the most common neonatal
tumors
• Discuss the work up for the
neonatal tumors
• Discuss the treatment approach to
neonatal tumors
• Show representative cases of
neonatal tumors
• Prevalence – 1:12,000 to 1:17,000
live births
Introduction
Introduction
• Diagnostic and management
challenge because of the wide
variety of locations and tumor types
• Benign tumors can be lethal and
malignant tumors can be very
treatable with operation only
• Lymphovascular malformations are
the most common tumor overall
encountered
• Teratomas are the #1 benign tumor
encountered
• Neuroblastoma is the #1 malignant
tumor encountered
• 1.9-2.6% of all pediatric
malignancies are diagnosed in the
perinatal period
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Introduction
Introduction
• Up to 70% will be diagnosed
prenatally via fetal U/S
• RADIUS trial demonstrated no
benefit in perinatal outcome or
survival, but did show U/S detection
did impact perinatal management
• Not all masses will be “cancer”, so
consider appropriate choice of
words
– Mass
– Growth
– Lump
– Bump
– Tumor
Tumor distribution
• Location
• Tumor
–
–
–
–
–
Teratoma
Lymphovascular malformations
Neuroblastoma
Fibrosarcoma
Rhabdomyosarcoma
–
–
Neuroblastoma
Teratoma
– Abdominal
–
–
–
–
–
Adrenal tumors
Mesoblastic nephroma
Teratoma
Liver tumors
Sarcoma
– Pelvic/genital
–
–
–
Teratoma
Fibroma/Sarcoma
Neuroblastoma
– Skin/soft tissue
–
–
–
–
–
Infantile fibrosarcoma
rhabdomyosarcoma
Neuroblastoma
Lymphovascular malformations
histiocytosis
– Head/neck
– Thoracic
Vascular Malformations
• Present at birth and grow commensurately with
the child
• Histologic examinations shows that there is no
cellular proliferation but rather a progressive
dilation of channels of abnormal mural structure
• They are lined by flat, quiescent endothelium
lying on a thin single laminar basement
membrane
• Divided into arteriovenous, venous, and
lymphatic
Head/Neck
Lymphangiomas
• Congenital malformations of lymph tissue that
result from the failure of lymph spaces to
connect to the rest of the lymphatic/venous
system
• Can occur anywhere in the body
• Head and neck region is the most common site
(75%) with axilla the second most common
(20%)
• Equal frequency in both sexes and among all
ethnic groups
• Divided into microcytic (capillary) and macrocytic
(cavernous)
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Lymphangiomas
• Clinical Presentation
– Usually discovered at birth (60%) and 90% found by
the age of one
– presents as a soft, smooth, nontender mass that is
compressible and can be transilluminated
– Symptoms related to the anatomic location of the
malformation and the extent of involvement of
adjacent structures
– Increase in size can result from infection or intralesional bleeding
• Also the two most common complications
Hemangiomas
Lymphangiomas
• Goal is to improve cosmetic appearance and
to counter impaired breathing or eating
– Sclerotherapy
• pure ethanol, sodium tetradecyl sulfate, doxycycline, and
OK-432
• Should be reserved for lesions of the head and neck, if <
5 cm, and if macrocytic
– Surgical resection
• offers the potential for "cure"
• should be undertaken with the understanding that these
are benign
• ideally removed in one procedure
MRI CHARACTERISTICS OF
VASCULAR ANOMALIES
• Typically involute by a year of age
• Resection versus observation dependent
upon location, if complications
(bleeding/ulceration/infection), and need
for diagnosis
T1 T2Contrast Gradient
Weighted Weighted (gadolinium)
Hemangioma
Soft-tissue mass,
isointense or
hypointense, flow
voids
Lobulated softtissue mass,
increased signal,
flow voids
Uniform intense
enhancement
High-flow vessels
within and around
soft-tissue mass
Venous
malformation
Isointense to
muscle, possible
high-signal thrombi
Septated softtissue mass, high
signal, signal voids
(phleboliths)
Diffuse or
inhomogeneous
enhancement
No high-flow
vessels
Arteriovenous
malformation
Soft-tissue
thickening, flow
voids
Variable increased
flow voids
Diffuse
enhancement
High-flow vessels
throughout
abnormal tissue
Lymphatic
malformation
Septated softtissue mass, low
signal
Soft-tissue mass,
high signal,
fluid/fluid levels
Rim enhancement
or no enhancement
No high-flow
vessels
Teratoma
• Most common neoplasm – 30-45% of all
tumors in the first month of life
• Rarely malignant (<5%) – platinum
based chemotherapy
• 20% of teratomas arise in the
head/neck
• Contain tissue elements from all three
germ layers (endo, meso, ectoderm)
• Treatment is operative removal
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Teratoma
• In the head/neck typically originate in
the thyrocervical area, palate, or
nasopharynx
• Usually will have polyhydramnios in
utero
• Can develop hydrops if large/vascular
• EXIT (ex utero intrapartum treatment)
procedure may be necessary
• Bimodal incidence
• 39 wk GA boy born by SVD
• Immediate respiratory compromise
requiring emergent intubation
• Obvious neck mass on physical
exam
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Thoracic
Thoracic masses
Teratoma
• Besides CPAM’s, pulmonary sequestrations,
congenital lobar emphysema, lung masses
are exceedingly rare
• 5% of teratomas arise in the thoracic
cavity
• Typically located in the thymus in the
anterior mediastinum
• Treatment is operative removal
• Teratomas and neuroblastomas account for
the majority of thoracic masses and are
located within the mediastinum
Neuroblastoma
• Derived from neural crest cells which
develop into the sympathetic ganglia
and adrenal medulla
• Despite being a malignancy, neonatal
neuroblastoma has a very good
prognosis and can undergo
spontaneous regression even if
metastatic (stage 4s)
• 40% will present in the first 3 months of
life
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Neuroblastoma
Case Presentation
• Second most common location for
presentation is in the posterior mediastinum
• Rarely have symptoms until quite large or
with metastatic disease
• The patient is a newborn male who was born
at 35 weeks gestation with immediate
development of respiratory distress and
required intubation
• Initial CXR concerning for hyperlucency of the
right lower lobe and possible mediastinal
mass
• CT scan performed
– Horner’s syndrome
– Spinal cord compression
– Respiratory symptoms
• Urinary HVA/VMA can aid in diagnosis
• Staging with CT, bone scan, bone marrow
biopsy
Figure 1: early radiograph showing right chest mass.
Figure 3: CT of mass with foraminal extension
Figure 5: liver hypodesities, suspicious for metastasis.
Figure 7
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Case Presentation
Case Presentation
• HVA – 66 (nl < 42)
• VMA – 108 (nl < 27)
• Given the lack of tissue needed for
complete staging, as well as the need to
keep him on antihypertensive
medications to control his blood
pressure, he was taken back to the OR
for attempts at a thoracoscopic
resection of the primary tumor
• Taken to the OR for bone marrow
bx, open liver mass bx, and CVL
Abdomen
Abdominal Tumors
• Adrenal - neuroblastoma
• Kidney – mesoblastic nephroma
• Liver – hemangiomas (60%),
mesenchymal hamartoma (23%), and
hepatoblastoma (15%)
Causes of antenatally
diagnosed adrenal masses
• Adrenal hemorrhage
• Enteric duplication cysts
• Subdiaphragmatic extralobar
pulmonary sequestration
• Adrenal cytomegaly
• Adrenocortical tumors
• Adrenal abscess
• Neuroblastoma
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Management of antenatally
diagnosed adrenal masses
Neuroblastoma
• Ultrasound evaluation and urinary
catecholamines recommended at
birth and at regular intervals
thereafter every 3 months until 1 yo
• MIBG and MRI scan within 9 weeks
• Biopsy if evidence of progression
• If >5 cm in diameter, operate
• Most common location is adrenal gland followed
by the organ of Zuckerkandl
• Urinary HVA/VMA can aid in diagnosis
• Staging with CT, bone scan, bone marrow biopsy
• 70% of neonatal neuroblastoma will be favorable
histology (not n-MYC amplified) and therefore
require no chemotherapy and achieve 95-100%
survival (stage 1 or 4s)
• 5% will be high risk and require intensive
multimodality therapy
– 30-50% survival
Case Presentation
Case Presentation
• Newborn male with prenatal diagnosis of a
left adrenal mass
• No symptoms
• MRI confirmed an 4 cm solid mass of the left
adrenal gland
• HVA/VMA slightly elevated
• Staging work up negative
• Repeat U/S in 3 months showed mass
enlarged to 8 cm and HVA/VMA increased
• 2 month old male with constipation since birth
and a enlarging mass on buttocks
• Physical exam notable for the mass overlying
the sacrum and rectal exam with large, firm,
non-mobile mass pushing the rectum
anteriorly
• AFP normal, HVA – 191 (nl <42), and VMA –
223 (nl<27)
• MRI done
Case Presentation
• Newborn male with massive abdominal
distention at birth and respiratory distress
• CT done confirming hepatomegaly and a left
adrenal mass
• Taken to the OR for biopsy
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Mesoblastic Nephroma
Case Presentation
•
•
•
•
• The patient is a 3 month old female born full
term after an uncomplicated pregnancy
• U/S at 20 weeks gestation reported to be
normal
• Seen at 2 month well baby check with no
abnormalities noted
• For the three weeks prior the mother began
having a difficult time putting on diapers
because of an enlarging abdomen
• Patient was otherwise in good spirits and
tolerating a diet
7% of all tumors in the neonatal period
Almost exclusively found under 6 months of age
Far outnumbers Wilm’s tumors in this age group
Develops from proliferating nephrogenic
mesenchyme
• No risk of invasion of renal vessels or IVC
• 90% are stage 1 or 2 and require no other
therapy besides radical nephrectomy
Primary liver tumors in the newborn
Malignant
Benign
• Infantile
hemangioendothelio
• Hepatocellular carcinoma
ma
• Mesenchymal
• Rhabdoid tumor
hamartoma
• Yolk sac tumor
• Hepatoblastoma
• Choriocarcinoma
• Undifferentiated sarcoma
• Rhabdomyosarcoma
•
•
•
•
•
•
Teratoma
Adenoma
Focal nodular hyperplasia
Hepatic cysts
Liver abscess
Inflammatory pseudotumor
Liver hemangiomas
• Classified as isolated, multifocal, or diffuse
• Most will involute by a year of age
• Frequently associated with hypothyroidism (iodothyronine
deiodinase in the tumors)
• Larger tumors associated with Kasabach-Merritt
syndrome
• MRI/CT diagnostic with early phase enhancement in the
arterial phase
• Medical treatment consists of propanolol (2-3 mg/kg/day),
followed by steroids (5 mg/kg/day), followed by vincristine
• Operative therapy if symptoms persist, medical treatment
fails, or unsure of diagnosis
• Mortality ranges from 12-90%
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Mesenchymal Hamartomas
• Benign tumors but reports of malignant
degeneration if left untreated
• Relatively avascular on U/S and
CT/MRI
• Most will have a cystic component to
them
• Most patients are asymptomatic with an
incidentally discovered mass
• Most occur in the right lobe
Case presentation
• 3 month old male presents to his
pediatrician for a well child check
• Liver is enlarged on exam
• U/S followed by a CT
Hepatoblastoma
• Most common liver malignancy in pediatrics
• Prematurity with low birth weight associated
with a 10-100 fold increased risk over the
general population
• Most occur 3-18 months of age
• Elavated alpha-fetoprotein in more than 90%
• Fetal subtype is most favorable
• Cisplatin based chemotherapy
• Transplant is an option for unresectable
disease
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Case Presentation
• The patient is 3 month old male who initially
presented to his primary care physician with
concerns about poor oral intake, constipation, and
"not looking right"
• A CXR was done and it was noted that his liver
appeared enlarged
• Concerns were now about a possible congenital
heart defect
• An ECHO was normal with the exception of a mass
within the liver
• This prompted an U/S followed by a CT
61
Case Presentation
• AFP 702,000
• Underwent a percutaneous biopsy
• He received cisplatin, doxorubicin, 5-FU,
vincristine
• AFP decreased to 313
• Repeat MRI
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Teratoma
Pelvic/Genital
• 1 in every 35,000 live births
• Tumors that contain elements derived from
more than one of the three embryonic germ
layers
• Contain tissue that is foreign to the anatomic
site in which they occur
• Can occur anywhere in the body and present
as cystic, solid, or mixed lesions
• Sacrococcygeal region is the most common
site (40%)
• Four times more common in females
Surgical Aspects
Types Altman
Classification
• Majority of the time can be excised through a
chevron buttock incision, but if significant intraabdominal component (Type III + IV) approach
through the abdomen first and then turn the
baby over
• Control the blood supply early
• Must excise the coccyx otherwise high
recurrence rate (>35%)
• Preserve all muscular and neural structures
even if very thinned/stretched out
Outcome
Outcome
• Survival dependent upon development
of intra-uterine hydrops and prematurity
• Recurrence 4-21%
• 50-70% of recurrences are malignant and
usually endodermal sinus tumors
• Follow-up every 3-6 months for the first
three years with rectal examination and
check of AFP level
• If recurrence then resection and if
malignant usually a platinum based
chemotherapy
• Approximately 25% of children followed
long term will have urinary or bowel issues
– Approximately 50% survival if diagnosis
made prenatal and associated with
maternal symptoms
• Overall risk of malignancy 13-27%
• Dependent upon time of presentation
– < 2 months has < 10% malignancy
– > 2 months has 50% malignancy
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Case Presentation
bladder
spine
• Newborn male noted on initial physical
exam to have an enlarged left testicle
• U/S performed confirming a solid mass
nearly replacing the normal testicle
teratoma
74
• Infantile fibrosarcoma
Skin/soft tissue
– 25% of soft tissue sarcomas < 1 year
– 5 year survival 95%
– 50% present at birth
– Rapid growth
– Usually located in distal end of
extremities
– Characterized by the translocation of
t(12;15)(p13;q25)
– Neoadjuvant (vincristine/actinomycin)
therapy prior to operation to spare
normal tissues
Management
• Biopsy indicated unless imaging
“classic” for vascular tumors
• Malignant tumors can mimic vascular
tumors
• U/S and MRI most often used for soft
tissue mass work up
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Original x-rays
Original x-rays
Original MRI
Original MRI
bones of
fingers
• Rhabdomyosarcoma
– 33% of soft tissue sarcomas < 1 year
– 5 year survival 60%
– 2% of cases present at birth
– Embryonal (70%) and alveolar (30%)
– Occurs in all body sites
– Symptoms vary based upon site
– Despite more “favorable” tumor,
neonates have worse outcomes for
“equivalent” disease
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Case presentation
• 3 week old male born with gastroschisis
• Undergoes primary closure and was on
advancing feeds when the mother felt a
“lump” on his back when she was
burping him
Case presentation
• 6 week old male in otherwise good
health was noted by his parents to have
a “bump” on his lower back when they
were drying him off after a bath
• Lymphovascular malformations
– Most common soft tissue tumors
– Can occur anywhere on the body
90
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91
THE END!!!
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