MINISTRY OF HEALTH OF TH REPUBLIC OF MOLDOVA [601058]
MINISTRY OF HEALTH OF TH REPUBLIC OF MOLDOVA
STATE OF MEDICAL AND PHARMACEUTICAL UNIVERSITY
―NICOLAE TESTEMITANU‖
FACU LTY OF MEDICINE
CATEDRA: CHIRURGIE, ORTHOPEDIE & ANES THESIO LOGY OF
PEDIATRIC
DIPLOMA THESIS IN GENERAL MEDICINE
TOPIC: ABDOMENAL TUMOR IN CHILDREN
AUTOR: Ashraf Laham
6th year, group.1638
Conductor:Prof.Dr.Eva Gudumac
Chisinau,2015
1
Aim of the research (scop ul):
The goal of the resea rch is to improve the medical and
surgic al treatment result in children with abdo menal
tumor by developing an algorithm for diagnosis and
prevention co mplication.
The research objective :
1. To study the epide miology and demograp hy of
abdomenal tu mors in children.
2. To optimize diagnostic t echniques and assess clinical
and laboratory features in abdomenal tu mor in children
3. To improve the medical and surgical management
of abdomenal tu mor in children
2 Statemen
t
I here by declare that the license thes is titled ―abdomenal tumors in children‖
is written by me and has never been submitted to another university or institution
of higher education in the country or abroad. Also, that all sources used, includ ing
those on the Internet, are given in the paper with the rules for avoiding plagiarism:
-all the fragment soft extreproduced exactly, even in his own translation from
another language are written between quotation marks and have a detailed reference
source;
-reformulation of the texts in own wordswritten by other authors have
detailed
referenc
e;
-summarizing the ideas of other authors have detailed referenceto the original
text.
Ashraf Laham
3 Table of Contents
List of figures…………………………. ………………………….. ………………………….. ………. 3
List of abbreviation …………………………. ………………………….. ……………………… . 4-6
CHAPTER 1 :INTRODUCTION…………………………. ………………………….. ……. 7-8
CHAPTER 2 : BACKGROUND …………………………. ………………………….. …….9-11
2.1 Abdomenal tumor definition …………………………. ………………………….. …………. 9
2.2 Symptoms …………………………. ………………………….. ………………………….. ….9
2.3 Causes and risk factors …………………………. ………………………….. …………… .9-10
2.4 Diagnosis…………………………. ………………………….. ………………………….. …….10
2.5 Treatment …………………………. ………………………….. ………………………….. .10-11
2.6 Prognosis …………………………. ………………………….. ………………………….. …….11
CHAPTER 3 : TYPES OF ABDOMENAL TUMORS…………………………. ….12-52
3.1 Renal and adrenal tumor in children …………………………. …………………………. .12
3.1.1 Neuroblastoma…………………………. ………………………….. ………………. .12-19
3.1.2 Pheochromocytoma…………………………. ………………………….. …………… .20-21
3.1.3 Adrenocortical tumor…………………………. ………………………….. …………. .21-23
3.1.4 Nephroblastomatosis …………………………. ………………………….. …………. .23-25
3.1.5 Mesoblastic nephroma …………………………. ………………………….. ……………. .25
3.1.6 Wilms’ tumor (nephroblastoma) …………………………. ………………………. .25-31
3.1.7 Clear cell carcinoma of the kidney …………………………. ………………………… .31
3.1.8 Rhabdoid tumor of the kidney …………………………. ………………………….. ……32
3.1.9 Renal cell carcinoma …………………………. ………………………….. …………. .32-33
3.1.10 Lymphoma and leukamia …………………………. ………………………….. ……….. 33
3.2 Liver tumors in children …………………………. ………………………….. ……….. .33-42
3.3 Pancreatic tumor in children …………………………. ………………………….. ……42-44
3.4 Gastrointestinal stromal tumor in children. …………………………. ……………. .44-48
3.4.1 Myofibromatosis …………………………. ………………………….. …………………… .48
3.4.2 Lymphoma…………………………. ………………………….. ………………………. .48-49
3.4.3 Carcinoid tumor …………………………. ………………………….. ……………….. .49-51
3.4.4 Colorectal adenocarcinoma …………………………. ………………………….. …..51-52
CHAPTER 4 : CASE HISTORY…………………………. ………………………….. …..53-67
CHAPTER 5 : CONCLUSION…………………………. ………………………….. …………. 68
REFERANCES…………………………. ………………………….. …………………………. .69-77
LIST OF FIGURES
Figure 1 : Invas ive or infiltrative localized tumor will be designated as L2 Loco
regional tumor not invading ad jacent organs will be classified as L1 disease.
15
Figure 2 : MRI image for Neuroblastoma …………………………. ………………………….. …………… .18
Figure 3 : MRI image for Phaeochromocytoma …………………………. ………………………….. …..21
Figure 4 : CT image of Adrenocortical tumor …………………………. ………………………….. …….. 22
Figure 5 : Ultrasonography image of Nephroblastoma …………………………. …………………… .24
Figure 6 : MRI image of Wilms’ tumor …………………………. ………………………….. ………………. 26
Figure 7 : MRI image of rhabdoid tumor…………………………. ………………………….. …………….. 32
Figure 8 : Ultrasongraphy image for Hepatocellular carcinoma …………………………. …….. 36
Figure 9 : CT scan with oral and IV contrast (Insulinoma) …………………………. ……………. .43
Figure 10 : CT scan Gastrointestinal tumor …………………………. ………………………….. ………… 45
Figure 11 : PET scan for Adenocarcinoma of descending colon…………………………. ……. 52
ABBREVIATIONS
HB -hepatoblastoma
HCC -hepatocellular carcinoma
FNH -focal nodular hyperplas ia
AFP -alpha fetoprotein
CBC -complete blood count
CT -computed tomography
MRI -magnetic resonance imaging
TSH -thyro id stimulating hormone
COG -childhood oncology group
IVC -inferior vena cava
5-FU -fluorouracil
FDA -food and drug association
UNOS -united network of organ sharing
GIST – gastrointestinal stromal tumor
WT -wild tumor
APUD – amine precursor uptake and
decarboxylation
5-HIAA -5 hydroxyindoleacetic acid
NBL – neuroblastoma
SIOPEN-R-NET -research network
VMA – vanillylmandelic acid
HVA – homovanillic acid
INSS -international neuroblastoma
T1W – t1 weighted
T2W -t2weighted
MIBG -metaiodobenzylguanid ine scintigraphy
MDP – methylene diphosphonate
DNA – deoxyribonucleic acid
ACT – adrenocortical tumor
DHEAS – dehydroepiandrosterone sulfate
CMN – congenital mesoblastic nephroma
SIOP – international society of pediatric
oncology
CCSK – clear cell sarcoma of the kidney
MEN – multip le endocrine neoplasia
VIP – vasoactive intestinal peptide
CHAP TER 1 :INTRODUCTION
Abdominal cancers include adrenocortical tumors, carcinomas of the stomach, cancer
of the pancreas, colorectal carcinomas, carcinoid tumors, and gastrointestinal stromal
tumors. The prognosis, diagnosis, classification, and treatment of these abdominal
cancers are discussed below. It must be emphasized that these cancers are seen very
infrequently in patients younger than 15 years, and most of the evidence is derived
from case series.[5]
A diagnosis of cancer represents a significant cris is for the child and their family. As
the treatment for childhood cancer has improved dramatically over the past three
decades, most children diagnosed with cancer today survive this illness. However, it is
still an illness which severely disrupts the lifestyle and typical functioning of the
family unit. Most treatments for cancer involve lengthy hospital stays, the endurance
of painful procedures and harsh side effects.[12] Research has confirmed that to
manage and adapt to such a crisis, families must undertake measures which assist
their adjustment. Variables such as level of family support, quality of parents’ marital
relationship, coping of other family members, lack of other concurrent stresses and
open communication within the family have been identified as influences on how well
families adjust to a diagnosis of childhood cancer. Theoretical frameworks such as the
Resiliency Model of Family Adjustment and Adaptation (McCubbin and McCubbin,
1993 , 1996) and the Stress and Coping Model b y Lazarus and Folkman (1984) have
been used to explain how families and individuals adapt to crises or adverse
circumstances. Developmental theories have also been posed to account for how
children come to understand and learn about the concept of illness. However more
descriptive information about how families and children in particular, experience and
manage a diagnosis of cancer is still needed.[26]
Cancer is, next to accidents, the second most common cause of childhood death in
developed countries The total inc idence of childhood cancer varies little throughout
the world. In Europe, approximately 1 in 5-600 children develop a malignant d isease
before the age of fifteen. A minor part of childhood cancers are caused by genetic
factors(Since the window for exposure is quite limited in childhood cancer, exposures
encountered in utero are likely to contribute to carcinogenes is. Thus, etio logic studies
have focused on exposures that occur during pregnancy for cancers that arise early in
life.[18]
Parental infertility and infertility treatment have been hypothesized as possible
risk factors for childhood cancer. The link is suspected since many infertile couples
may have specific genetic or epigenetic anomalies that could be passed on to their
children, which in turn could lead to carcinogenes is.) but the aetio logy of most
childhood cancers remains unkn own. cancers differ markedly from adult cancers in
their nature, distribution and prognosis. Carcinomas are most common in adult
cancers, whereas haematological malignancies and tumours of the central nervous
system (CNS) account for the majority of childhood cancers Childhood cancers tend
to have short latency periods and to grow rapidly.[9]
Owing to specific diagnostic procedures and multimodal treatment strategies, the past
decades have seen a welcome, marked rise in the probability of cure for all cancer
.The overall survival rate for childhood cancer has risen dramatically. Childhood
cancer has extens ive consequences and places a heavy physical and psychological
burden on the child and its family. Rapid diagnosis helps ensure appropriate and
timely therapy and optimizes the chances of cure[51]
CHAPRET 2:BACKGROUND
2.1 Abdominal tumor difenition
An abdominal tumor is an irregular mass of abnormal cells that is located in the
middle of the body, including the stomach, abdominal tumor,and parts of the
intestines. They can be either benign, which is usually slow growing and harmless;
malignant, which is cancerous; or pre-malignant, which could turn into cancer. The
causes, symptoms, and treatment for these growths can vary greatly, but cancers
related to this area often have a poorer prognosis than many other types. Common
types of intra-abdominal masses inc lude kidney, colon, pancreatic, bladder,
neuroblastoma, and ovarian tumors, as well as cysts and abscesses. [48]
2.2 Symptom
Tumors in the abdomen usually don't create many obvious symptoms, especially
when they're in the early stages. If the mass grows or spreads, a person may
experience swelling and pain, d iarrhea, weight loss, nausea, vomiting, bad breath, and
digestive problems. A malignancy may also cause fatigue, fever, and blood in the
stool. Some types of tumors have more specific symptoms associated with them: for
instance, people with liver masses often become jaundiced, and those with ovarian
cancer may have painful menstruation or pain during intercourse. Likewise, those
with bladder growths may have a hard time urinating, and those with kidney cysts
often have high blood pressure[22]
2.3 Causes and Risk Factors
The causes and risk factors for abdominal masses generally include things that stress
ordamage the organ they're in or around. For instance, persistent heartburn or ulcers is
a risk factor for stomach cancer while having hepatitis or chronic alcoholism raises a
person's chances of liver tumors. Besides this,the general risk factors for most cancers
also apply. Family history may p lay a role, along with environmental concerns, such
as exposure to toxic chemicals or pollution. Poor diet, lack of exercise, smoking and
stomach polyps may also heighten the risk of getting an abdominal tumor. Regular
exerc ise and a healthy diet, which includes the antioxidants found in many fruits and
vegetables, may help reduce the risk for developing a mass. [37]
2.4 Diagnosis
Since most abdominal tumors don't cause symptoms, many are inadvertently
discovered by a healthcare professional during a routine med ical exam.Further
evaluation is typically needed to gather information about the mass and determine if it
even is a tumor, since things like swollen organs or fecal impactions can feel similar.
A Computer Tomography (CT) scan or Magnetic Resonance Imagining (MRI) study
is commonly used to get a clear picture of the growth. A b iopsy and blood tests may
be needed to determine if a mass is benign, malignant or pre-malignant.[1]
Healthcare providers can also use information from patients about the location of
tenderness or pain to help narrow down the type of growth they have. They generally
divide the abdomen into 4 quadrants — right upper, right lower, left upper, and left
lower — and may also describe a mass as epigastric, meaning that it is in the area just
below the ribs, or periumb ilical, meaning that it is in the area around the navel. If a
patient reported having epigastric pain, he or she might have a pancreatic mass, while
if he or she reported having pain in the right upper quadrant he or she might have a
liver cyst.[16]
2.5 Treatment
The specific treatment for an abdominal tumor depends on several factors, including
the type, size, location, and cause of the growth, and whether it has spread. Healthcare
providers typically perform surgery to remove a malignant abdominal tumor. In these
cases, treatment providers usually combine surgery with other cancer treatments, such
as chemotherapy and radiation therapy.[34]
Although less serious than a malignancy, a benign mass may still require treatment. If
it is large enough, it could interfere with nearby organs or regular bodily functions,
such as digestion, so surgical removal may be needed. Usually, benign tumors do not
grow back or require further treatment after being removed.[13]
2.6 Prognosis
A cancerous tumor in the abdomen can be a serious and life-threatening problem — in
fact, stomach cancer is one of the deadliest forms of cancer. [40] This is mostly
because noticeable symptoms do not occur until the disease is quite advanced. For this
reason, healthcare providers typically evaluate any lump found in the area. Even if a
mass is small and not causing problems, it is better to be cautious, because if a tumor
is malignant, an early diagnosis and prompt treatment may lead to a better prognosis.
CHAP TER 3:TYPES OF ABDOMINAL TUMOR
3.1 Renal and adrenal tumors in children
3.1.1 Neuroblastoma
Neuroblastoma (NBL) along with ganglioneuroblastoma and ganglioneuroma
constitute a group of ganglion cell origin tumours that originate from primord ial
neural crest cells, which are the precursors of the sympathetic nervous system. The
degree of malignancy is designated by the degree of cellular and extra-cellular
maturation of these tumors. The most undifferentiated and aggressive NBL presents in
young children (med ian age ≤2 years). The more mature tumor type is
ganglioneuroma which affects older age gro ups. NBL accounts for 8–10% of
childhood cancers. The two main prognostic factors are age and stage of disease at
presentation .Localized NBL and those arising in infants have a 90% survival rate
except in cases with Myc-N amp lification where survival is below
30%.Approximately 50% of NBL occurring in children older than 18 months of age
are metastatic at diagnosis.[30]
NBL is the second most common abdominal neoplasm in children following Wilms'
tumor and overall the third most common pediatric malignancy, after leukemia and
central nervous system tumors .It accounts for almost 15% of childhood cancer
fatalities, a number that reflects its aggressive nature and frequency of metastatic
disease. Most NBL deaths occur within 2 years of diagnosis. More than 90% of the
diagnosed cases are children aged less than 5 years. NBL protocols in Europe come
under the new SIOPEN-R-NET (Research-Network), which is attempting the remote
uploading of DICOM files onto a server for later central review. Infant NBL,
localized unrespectable NBL and high -risk (metastatic or MycN positive tumors)
studies are currently in progress.[7]
NBLs arise from the adrenal glands, the organ of Zuckerkand l or follow the
distribution of the sympathetic ganglia along para-spinal areas from the neck to the
pelvis. The most common primary site for NBL development is the retro peritoneum,
the adrenal medulla (35%) and the extra -adrenal paraspinal ganglia (30–35%),
followed by the mediastinum in 20%. Less common sites are the pelvis (2–3%) and
the neck (1–5%). Occasionally, in the presence of metastatic disease, no definite
primary tumor can be found.[32]
Clinical features
The most common (30–50%) malignancy encountered in the first month of life is
NBL. The majority of children with NBL however, present between 1 and 5 years of
age with a palpable abdominal mass. This may be an incidental finding in an
otherwise healthy child or in a child clearly unwell (from widespread dissemination of
tumor). NBL has overall a wide spectrum of clinical symptoms which depend on the
site, extent and the biological features of the primary tumor, and the presence of
distant metastatic disease. In half of the patients with intra-spinal tumor extens ion,
peripheral neurologic defic its and neurological symptoms from compression of the
nerve roots or the cord may be present. Subcutaneous dark purple or blue metastatic
nodules, the so-called ―blueberry muffin‖ skin, may be visib le. Metastatic
involvement of the periorbital bones and soft tissues results in ecchymosed orbital
proptosis, which is also described as ―raccoon eyes‖ and may be misinterpreted as
non-accidental injury. Compression of the optic nerves by metastases may cause
blindness. Massive hepatic metastases can cause increased intra-abdominal pressure
and death from respiratory insufficiency. Bilateral cystic NBL and acute intracystic
hemorrhage in infancy have also been reported. Encephalopathic symptoms may be
encountered. Cervical NBLs usually manifest as an isolated neck mass, stridor, or
dysphasia. Horner's syndrome may be present at presentation or develop post-
operatively from disruption of the sympathetic chain in the neck. In less than 2%,
NBLs can present with para-neoplastic syndromes: opsoclonus -myoclonus-ataxia
syndrome or watery diarrhea. NBLs may also be discovered incidentally during
scanning for other reasons, e.g. antenatal ultrasound, chest radiograph for pneumonia
or screening protocols.[47]
Infant screening
Screening with measurements of urinary vanillylmandelic acid (VMA) and
homovanillic acid (HVA ) levels in 6-month-o ld infants began in Japan in 1973 .
Unfortunately, epidemio logic analyses showed that this did not alter the inc idence of
tumor in older children nor did it improve cure rates. However, it was soon realized
that the incidence of stage 1 d isease dramatically increased, and that the tumors
discovered at screening were of low stage and favorab le histological characteristics. It
is assumed that similar numbers of NBL tumors occur in unscreened infants most of
which regress spontaneously. Consequently, widespread screening in other countries
has not been adopted and screening for NBL has been discontinued in Japan. The
impact of screening in children >1 year of age, however, remains unknown. [4]
Staging
The formal clinical staging system for NBL, the International Neuroblastoma Staging
System (INSS), was framed from a consensus international group in 1986 and revised
in 1993 (Tab le (Table1).1). It is widely accepted, uses the pattern of disease spread as
determined by radiographic and scintigraphic studies, surgical operability, lymph
node and bone marrow involvement, and is useful for tumor prognostication and
comparison of treatment results. The new so-called Whistler criteria for International
NBL R isk Grouping (INRG) may nevertheless replace the standard INSS staging for
NBL in childhood. These modifications, currently being finalized, will categorize
NBL into low, intermediate and high risk groups. High risk groups will include
metastatic tumors (other than infantile 4S disease) and all Myc -N amplified tumors
irrespective of age. The age cut-off for 4S disease will probably be increased to 18
months. Risk grouping will be dependent on pre-operative imaging rather than post-
surgical staging (H. Brisse, personal communication). [10]
Figure. 1
Invas ive or infiltrative localized tumor will be designated as L2 Loco regional tumor
not invading adjacent organs will be classified as L1 disease.
Neuroblastoma. (a) Axial post-contrast CT section showing a typ ical heterogenous
calcified supra-renal mass encasing the retroperitoneal vasculature and displacing the
pancreas anteriorly. (b) Coronal CT showing a large mass of mixed attenuation and
calcification…
International Neuroblastoma Staging System (INSS)
Localized tumor are currently divided into stages 1 and 2, based on regional lymph
node status (contra lateral nodes being a criterion for stage 3 disease). Unrespectable
tumors which extend across the midline at least as far as the contra lateral pedicle of
the vertebral column are classified as stage 3 disease. Mid line extens ion is often a
feature of large, locally invas ive tumor that encases vital vascular or neural structures.
Stage 4 refers to all patients diagnosed with distant disease (lymph nodes, bones, bone
marrow, liver and other organs). A special category in INSS is stage 4S disease,
where S stands for special. It refers to infants <1 year of age with small, localized
primary tumor and dissemination limited to the liver, skin or bone marrow but no
distant osseous metastases. In bone marrow aspirates tumor cells are rare (<10%).
Nevertheless, the distinction between the stage 4 types is somewhat arb itrary and can
be confusing in children <1 year of age. As mentioned above, the age cut-off of 12
months may soon be changed to 18 months regard ing 4S disease. Quantification of
marrow and liver invo lvement (e.g. differentiation between ―diffuse heterogeneous‖
in 4S and ―numerous‖ liver metastases in the poorer forms of stage 4) is difficult,
resulting in a grey area of overlapping rad iological findings. Despite metastatic
spread, 4S tumors virtually always have favorable bio logic behavior and survival rate
>90%. A more recently recognized variant of NBL, stage 4N has been described and
is not inc luded in the INSS classification. This has been proposed fo r children with
distant nodal spread, but no cortical invo lvement, on account of their seemingly better
prognosis.[69]
Neonatal suprarenal masses
Antenatal suprarenal masses may be congenital NBL but the sonographic appearances
are variab le and different ial diagnosis includes mesoblastic nephroma, extra -lobar
pulmonary sequestration and adrenal hemorrhage. A right-sided location, diagnosis in
the third trimester, and cystic or mixed echogenicity, often help differentiate NBL
from an intra-abdominal sequestration. Without pathologic proof, it is not possible to
differentiate an adrenal hemorrhage from a spontaneously resolving NBL and non-
invas ive monitoring of these small supra-renal lesions with repeat ultrasound
examinations and measurement of urinary catecholamine levels are advocated. Fetal
NBL has a very good prognosis, and treatment may be conservative. [11]
Imaging features
Ultrasonography (US) is the initial imaging modality to investigate an abdominal
mass. On US, NBLs are heterogeneous solid lesions. Cystic anechoic areas are much
less common in NBLs than in Wilms' tumour. Calcification is common but variable in
appearance. The ipsilateral kidney is usually d isplaced by the large retroperitoneal
tumor, and its identification facilitates differentiation from Wilms' tumor. The aorta
and inferior vena cava (IVC) are usually displaced anteriorly and together with the
portal vein, the celiac axis, the mesenteric and the renal vessels may be surrounded by
the les ion. Vessel patency should be evaluated with color Doppler US. Metastatic
involvement or invasion of the liver can be detected with US. The typical finding
suggesting invas ion of the liver by the mass is the absence of differential movement
between them.[29]
NBL staging requires additional multi-modality imaging. CT or MRI, [123I]meta-
iodobenzylguanid ine (123 -MIBG), and laboratory investigations (bilateral bone
marrow aspirates with histochemical tests and urine catecholamine level
measurements) all need to be performed. Additional routine 99m
-methylene
diphosphonate bone scan (99m
-MDP) is also advocated by many. Overall MRI has
become the most useful modality in staging of NBL. MRI is superior to CT in
determining marrow infiltration and intra-spinal extens ion of tumor. Bone marrow
disease is usually seen as diffuse infiltration but it may also present a nodular pattern
with areas of low and high signal intens ity on T1-weighted (T1W) and T2-weighted
(T2W) images, respectively[26]
Figure. 2
Neuroblastoma. (a) Axial T2W MRI showing a large upper abdominal primary. (b)
Planar MIBG scan showing a solitary metastas is in the sacrum superior to isotope in
the bladder (arrows). Note the primary upper abdominal tumor is also MIBG avid.
The lower…[49]
MIBG shows almost similar results with bone marrow aspirates in detecting bone
marrow infiltration and could be considered more sensitive since it has the advantage
of depicting the whole skeleton. MIBG is probably as sensitive as magnetic resonance
imaging (MRI) in detecting bone marrow invo lvement during initial staging but more
specific than MRI in evaluating response to treatment (F ig.2). Benign
ganglioneuromas may also take up MIBG and cannot be differentiated from active
NBL. MIBG scans offer additional prognostic information: a poor outcome has been
associated with MIBG-positive scans in stage 4 patients >1 year after presentation,
and in those patients remaining positive after induction chemotherapy. The same
correlation was not seen with concurrent MDP bone scans. Disappearance of all
metastatic foci on MIBG scanning is commonly regarded as complete response (CR)
in NBL staging and follow-up. Semi-quantitative MIBG scoring systems are now in
place for many metastatic NBL studies. The achievement of a CR of the metastases is
one of the strongest prognostic factors. When CR is achieved it is also common
practice for the residual primary tumour to be resected when possible.[20]
Treatment and prognosis
Chemotherapy is indicated in localized NBL, particularly with larger primary tumors,
in order to attempt a safe surgical exc ision. Prognosis of NBL, which even includes a
propensity to spontaneous regression in infancy, is influenced by several parameters,
such as tumor proto-ontogenesis, DNA content, and catecholamine synthesis. Use of
these parameters enables tumor categorization into low-, intermediate-, or high-risk.
Therapeutic strategy strongly depends on initial staging with multi-modality imaging
and constitutes surgery where possible, chemotherapy in the majority, while bone
marrow transplant has been recently introduced. High dose chemotherapy followed by
hematopoietic stem cell transplantation, and maintena nce therapy with retinoic acid,
improves survival by 35% in children presenting with metastatic NBL, but the 5-year
event-free survival remains below 50%. Radiotherapy is now used in Europe for high-
risk disease patients (treating only the primary site) after chemotherapy. It is also used
occasionally as palliation for painful bone metastases and for hepatomegaly from 4S
disease that compromises respiratory function. High-dose MIBG therapy is used in
selected relapsed stage 4 patients. Children with stages 1, 2, and 4S tumors have 3-
year event-free survival rates of 75–90%. Children older than 1 year with INSS stages
3 and 4 tumors have 3-year event-free survival rates of 50% and 15%, respectively[3]
3.1.2 Phaeochromocytoma
Phaeochromocytomas are a type of paraganglioma which arise from the adrenal
medulla. However, up to one-third of phaeochromocytomas (extra-adrenal
paraganglio mas) may occur in the sympathetic chain of the neck, mediastinum or
abdomen. They are generally sporadic in childhood, usually occurring in adolescence.
A minority are associated with multiple endocrine neoplas ia syndromes (mostly type
2), von Hippel–Lindau syndrome or neurofibromatosis. Approximately 10% of
sporadic tumors are multip le in locations, b ut the inc idence of multiple tumors rises to
30% in the inherited cancer syndromes. Ten percent of tumors are malignant. In
children, hypertension is nearly always sustained rather than paroxysmal. Headaches,
sweating, nausea and vomiting are common presenting features. Postural hypotension
is also frequently encountered. Diagnosis depends on raised plasma catecholamines
and increased urinary catecholamines, and their metabolites (urinary epinephrine,
metanephrine, HVA , VMA). Abdominal US should be the firs t radiologic
examination. MIBG scanning must be performed next (Fig.3). MIBG may be positive
in the abdomen even when an US is negative and MIBG should always be done prior
to surgery to detect or exclude multip le sites of disease. Computed tomography (CT) ,
or preferably MRI, are useful for surgical planning after MIBG scintigraphy.
Adrenergic blockade, to prevent a hypertens ive cris is, is not required prior to non –
ionic contrast administration during CT scanning. Phaeochromocytomas typically
show intense enhancement after contrast administration at both CT and MRI. These
tumors are also characteristically marked ly hyperintense on T2W MRI (Fig. 3).
Surgical resection is curative in benign disease.[25,70,2]
Figure 3.
Phaeochromocytoma. (a) Although this is probably not an adrenal primary, this left-
sided phaeochromocytoma mass shows typical hyperintens ity on T2W MRI. (b) The
tumor also characteristically takes up MIBG. This was a solitary tumor. [18]
3.1.3 Adrenocortical tumors
Adrenocortical tumors (ACT) are very rare in children with a worldwide annual
incidence of 0.3 per million children below the age of 15 years. Curiously there
appears to be a 15 times higher frequency of ACTs in southern Brazil (most of these
children have a p53 germline mutation). The incidence is higher in young girls with a
female/male ratio of 2:1, whereas in adolescence the sex ratio is equal. Virilisation,
with early onset of pubic hair, hypertrophy of the clitoris or penis, accelerated growth,
gynaecomastia or acne, is the most common presentation. The second most common
manifestation is with hypercortisolism (Cushing's syndrome), whilst presentation with
a palpable abdominal mass is unusual. Cushing's syndrome is a relatively more
common presentation in adolescents and young adults. Very few tumors are non-
hormone secreting in contrast to ACTs in adults. Hypertens ion may be seen in up to
43% at diagnosis. This may be due to either mineralocorticoid or glucocorticoid
excess, increased aldosterone production or simply renal artery compression by the
tumor, and the hypertension usually resolves after tumor resection. Diagnosis of an
ACT is supported by raised levels of androstenedione, dehydroepiandrosterone
sulphate (DHEAS), testosterone, and urinary steroids. These hormones are also useful
markers for the detection of tumor recurrence during follow -up. Two syndromes have
a clear association with this tumor: Li–Fraumeni syndrome is associated with
mutations of the p53 gene, and Beckwith–Wiedeman which has mutations in the
11p15 region. Ultrasound is the first line investigation and is particularly useful in
evaluating for IVC tumor invasion. With a negative ultrasound and the appropriate
clinical context an MRI should also be performed as left adrenal masses in particular
may be difficult to visualize with US. Where MRI is unavailable CT may be
performed (Fig.4). Chest CT to exclude or detect p ulmonary metastases should be
performed at first diagnosis.[41]
Figure 4.
Adrenocortical tumor (ACT). Axial CT section post-contrast enhancement shows a
small soft tissue mass immed iately to the right of the aorta (arrow), due to an
unfortunate recurrence of an original right adrenal ACT. [52]
The classification of benign from malignant ACTs is not clear cut and is the subject of
much debate. Differentiation between adenoma and carcinoma is in practice
somewhat arbitrary, and all patients (even those with a seemingly benign adenoma
completely resected) require close follow-up initially. On occasions it is
recommended to classify the tumour as an ―atyp ical adrenocortical neoplasm‖ or
―adrenocortical neoplasm of indeterminate malignant potential‖. The majority of
ACTs in children are interpreted pathologically as malignant in most studies. Factors
favoring malignancy inc lude size over 5–10 cm, weight over 200 g, invasion into the
periadrenal soft tissues or IVC.[17]
Surgical resection is the mainstay of treatment. Lymph node biopsy should be
performed in all cases and radical lymph node dissection may be necessary in some
malignant cases. The role of radiotherapy is uncertain. Similarly the role of
chemotherapy is limited with many centres using mitotane, as in adult ACTs, but its
efficacy in children has not been well studied. Younger children, particularly those
less than 5 years, with pathologically malignant ACTs, have a significantly better
prognosis than older children and adolescents.[33]
3.1.4 Nephroblastomatosis
The term ―nephrogenic rest‖ imp lies persistence of embryonic renal parenchyma
(metanephric blastema) beyond 36 weeks gestation. Nephroblastomatosis is the
presence of multip le nephrogenic rests. These abnormal foci of persistent nephrogenic
cells are regarded as precursor lesions. There is an increased incidence of Wilms'
tumor (―nephroblastoma‖) in children with nephroblastomatosis. The lesions are
found in approximately 40% of unilateral Wilms' tumors, and 99% of multicentric or
bilateral Wilms' tumors. The malignant potential of ind ividual lesions is uncertain as
only a minority of nephrogenic rests develop into Wilms' tumors and spontaneous
regression may occur.[8]
Imaging features of Nephroblastomatosis
Nephroblastomatosis may either be diffuse or multifocal although a unifocal form
may be found. The diffuse form typ ically manifests as a thick hypoechoic band on US
(Fig. 5a). This abnormal tissue surrounds the renal periphery and is non-enhancing on
CT and MRI (Fig. (Fig.5b,c). In the more common multifocal type, the nephrogenic
rests resemble normal renal cortex on all modalities and can be scattered throughout
the kidneys; they may be nodular or plaque-like and after contrast administration they
become hypodense on CT and hypointense on MRI due to poor perfusion in relation
to the highly vascular renal cortex.[57]
Figure 5
Nephroblastomatosis. (a) Longitudinal ultrasound showing marked renal enlargement
in a 1-year-o ld with widespread hypoechoic change in the renal parenchyma due to
diffuse nephroblastomatosis. (b) Fat-suppressed post-gadolinium enhanced MRI. The
two plaque-like…[6]
Nephroblastomatosis has variable signal intensity depending on cellularity and
histologic characteristics on T2W images. In general, the signal intensity of
nephroblastomatosis on all sequences, includ ing gadolinium-enhanced images, tends
to be relatively homogeneous in contrast to Wilms' tumors which are always
heterogeneous in appearance. Contrast administration is mandatory in the assessment
for nephroblastomatosis as the lesions are always much more conspicuous on post –
contrast studies, most notably after gadolinium administration for MRI. Despite fairly
characteristic imaging appearances, if a les ion enlarges then early histological
evaluation is warranted and serial as sessments are necessary because of the known
malignant risk.[19]
It is hypothesised that MRI may be able to distinguish a sclerotic from a hyperplastic
nephrogenic rest. Sclerotic rests are thought to be in a regressive phase and to thus
lack the potential to develop into a Wilms' tumor. Sclerotic rests typically appear dark
on T2W MRI, whilst hyperp lastic rests are usually hyperintense on T2, similar to
Wilms' tumor. It is less important to distinguish a Wilms' tumor from a hyperplastic
rest as the latter has the potential to develop into a tumor and also the capacity to
enlarge. In the setting of bilateral nephroblastomatosis or bilateral Wilms' tumors on
treatment, it is thought that hypointense lesions on T2 (sclerotic rests) may simply be
observed, whereas hyperintense les ions on T2 may require further chemotherapy or
local resection. CT is unable to make this distinction. [56]
3.1.5 Mesoblastic nephroma
Mesoblastic nephroma, also known as congenital mesoblastic nephroma (CMN), is
the most common renal neoplasm in the first 3–6 months of life. It typ ically presents
as an abdominal mass in a neonate. On US, the mass is solid but there may be
hypoechoic areas due to cystic change or necrosis. Neither US nor CT can reliab ly
distinguish CMN from Wilms' tumor. The benign CMN does not invade the vascular
pedicle nor does it metastasise. Local recurrence may result from incomplete removal
or capsular penetration. With complete removal there is an excellent prognosis. [58]
3.1.6 Wilms' tumor (nephroblastoma)
Wilms' tumor (nephroblastoma) is the most common malignant primary renal tumor
in childhood. Wilms' tumor accounts for up to 12% of all childhood cancers with a
peak incidence at around 3 years of age (F ig.6). The commonest presentation is an
asymptomatic abdominal mass. Haematuria, particularly after minor trauma, is
another typical clinical manifestation; pain, fever or hypertens ion (in up to a quarter
of cases) are unusual but recognised presenting features. Microscopic haematuria is
present in 25% of cases. There is equal distribution between the sexes with the highest
incidence being in the black population in the USA and Afric a. Around 10% of
Wilms' tumors are bilateral, of which two-thirds are synchronous and one-third
metachronous.[43]
Figure 6.
Wilms' tumor. (a) Longitudinal ultrasound showing a very cystic Wilms' mass which
had few solid components. (b) Axial T1W MRI after gadolinium-enhancement
showing a large heterogenous left renal tumor, with a reasonably well-defined
―capsule‖. …[10]
Associated conditions
Associated congenital anomalies occur in 15% of children and include cryptorchidism
and horseshoe kidney (Fig.6c). Certain syndromes have a predisposition to Wilms'
tumor. These include anirid ia (absence of ophthalmic iris), Beckwith–Wiedemann
(macroglossia, exomphalos, gigantism), hemihypertrophy, Denys –Drash
(pseudohermaphroditism), Soto's (cerebral gigantism), Bloom's (immunodefic iency
and facial telangiectasia) and Perlman's syndromes. In Denys –Drash syndrome, for
examp le, most but not all patients will develop a Wilms' tumor, the median age at
presentation being 18 months, and 20% of cases are bilateral. The role of routine US
screening to detect tumors at an early stage in Beckwith–Wiedeman syndrome in
particular is debated because interval tumors may occur between US studies, and
tumors are always of favorab le histo logy and chemosensitive. As screening in high
risk cases has tended to be erratic in the UK (if not the entire world) a national
screening program has been instituted to screen children with a greater than 5% risk
of developing a Wilms' tumor up to 7 years of age.[31]
A small group of Wilms' cases are familial. Intralobar nephrogenic rests are
commonly found in such patients but there is no association of familial tumors with
bilaterality. Extra-renal Wilms' tumors are rare; the most common locations are the
retroperitoneum, inguinal region and pelvis. Their histo logy and outlook are identical
to that of renal Wilms' tumors.[3]
Histopathology
Wilms' tumors are solid lesions with a fibrous pseudocapsule and have variab le areas
of hemorrhage and necrosis. The tumor may invade the renal vein and IVC with caval
extens ion, often to the right atrium, seen in 4% of patients. Metastases to local para-
aortic lymph nodes and haematogenous spread to the lungs and less commonly the
liver are seen. Epithelial (tubular, glomerular), stromal (spindle, myxoid) and
blastemal (small round cells) cell lines are the histologic components of nephrogenic
rests, fetal kidneys and Wilms' tumors. When all three are present in malignant
masses, the les ions are termed triphasic Wilms' tumors and are regarded as favorable
histology. These lesions lack anap lastic changes. Unfavorable tumors comprise 6% of
les ions and typically have hyperchromatic cells with large nuclei. The degree of
anaplasia correlates with patient outcome. Minimally anap lastic tumors have a
prognosis similar to favorable histology lesions.[50]
Staging
The (post-surgical) staging of Wilms' tumor according to the North American
National Wilms' Tumor Study Group is summarized below:
Stage I: tumor confined to the kidney without capsular or vascular invasion.
Stage II: tumor beyond renal capsule, vessel infiltration or intraoperative tumor
rupture.
Stage III: positive lymph nodes in the abdomen or pelvis, peritoneal invas ion or
residual tumor at surgical margins.
Stage IV: metastatic disease outside the abdomen or pelvis.
Stage V: bilateral tumors at original diagnosis. [66]
In Europe and elsewhere the International Society of Paediatric Oncology (SIOP)
utilises the same staging system with one exception – masses that have been biopsied
may be regarded as stage I disease when later excised (if confined to the kidney) but a
biopsy upstages a tumor to stage III disease in North America. An additional
disadvantage of renal b iopsy is that many anaplastic tumor are und iagnosed until the
time of nephrectomy, particularly those with focal anap las ia. Whether a renal tumor
merits biopsy prior to treatment is also debated but is routine practice prior to
chemotherapy in the UK. Some European centres omit biopsy for presumed Wilms'
tumors in early childhood, but at a cost of administering chemotherapy to 12% of
children with renal masses who, after nephrectomy, are proven not to have a Wilms
tumor. [61]
Imaging features
US must be the first radio logical method of assessment. The tumor typ ically is large
with a mixture of solid hyperecho ic masses and cystic areas with often the cystic
components predominating. Normal native renal tissue can be difficult to detect and is
typically stretched at the periphery of the les ion. Movement of the mas s separate from
adjacent organs such as the liver, ind icating a lack of direct invas ion, can be optimally
assessed with US, a phenomenon that is difficult to evaluate on CT or MRI. The renal
vein, IVC, liver and opposite kidney should be carefully assessed for spread of
disease. US is also the most reliable method of excluding renal vein and IVC
thrombus.[24]
Contrast enhanced CT or MRI is generally deemed necessary for further delineation
of tumor extent but it is noteworthy here that many lead ing European centers perform
only US at diagnosis and follow-up in their children with renal tumors with no
apparent detriment to patient care. On CT and MRI a tumor enhances to a lesser
degree than normal renal parenchyma. A so -called claw or beak sign of normal renal
tissue may be seen displaced by the tumor. Exclusion of adenopathy, liver
abnormalities, peritoneal invas ion and contra lateral kidney changes should be
undertaken. Contrast-enhanced images are required to assess the contra lateral kidney
for nephroblastomatosis in particular or another small Wilms' mass.[20]
Pulmonary metastases
There is continuing uncertainty among the pediatric collaborative onc ology groups
regard ing the optimum staging approach in patients with small lung les ions. Although
many such small (5–10 mm) lesions are metastases, a substantial minority are not.
Until recently the commonly used staging systems for pulmonary metastases were
based solely on chest rad iographs, such that positive find ings on CT were ignored if
no lesions could be visualized on a chest x-ray. The rationale for this was that[11]
chemotherapy for local disease ―mopped up‖ the possible small tumor burden within
the chest. However, some limited evidence suggests those with CT positive nodules,
negative on chest x-ray, have a higher relapse rate. In addition, inconsistency in
staging meant that in some centers when small nodules were identified on CT, these
patients were more intens ively treated as stage 4 disease, contrary to protocol. Local
stage 1–2 disease merits only two-drug chemotherapy, whereas stage 4 disease
warrants three drugs (with the addition of doxorubicin). But the optimal treatment
paradigm for small bulk disease in the chest is unresolved also. The role of
radiotherapy in particular is widely debated. Fewer relapse after lung irrad iation but at
a cost – more deaths from lung toxic ity and more long-term morbid ity. Within the
latest North American (Children's Oncology Group (COG), from 2006 ) study the
staging of metastatic disease will be done by central review. In the next COG Wilms'
study, the initial response to therapy by lung nodules will determine subsequent
pulmonary specific therapy. Lesions that disappear after 6 weeks of chemotherapy
will not require irrad iation. Persisting lesions after chemotherapy will be biopsied and
if positive for tumor will receive radiation therapy. In the current SIOP Wilms' tumor
study, lung CT is also now recommended. In that study, lesions must measure over 10
mm on CT to be defined as metastases (but whether these are to be measured on a
typical lung or mediastinal window setting is not stipulat ed).[48]
Treatment and prognosis
The treatment strategy of Wilms' tumors has become a model for the successful
multid isciplinary approach to pediatric solid tumors. The prognosis for most children
with Wilms' tumor is now so good that it is difficult to conduct a randomized trial
with adequate power to detect a magnitude of difference that might be clinically
significant. North American practice is initial surgical removal of the tumor followed
by adjuvant chemotherapy dictated by the staging found at surgery. European
oncologists favor initial chemotherapy (after biopsy confirmation in the UK) with
later resection. The optimal surgery inc ludes a transperitoneal approach with biopsy
of adjacent regional lymph nodes, whether enlarged or not. Nephrectomy is usually
carried out except in the setting of bilateral Wilms' tumors where partial
nephrectomies, when possible, are ind icated to preserve as much normal kidney tissue
with the hope of avoiding or delaying the subsequent onset of chronic renal failure.
The prognosis for Wilms' tumor patients is excellent and there is little evidence to
suggest that the overall relapse-free survival is adversely affected by either approach.
The 4-year overall survival rate, and presumed cure, ranges between 86% and 96% for
stages I–III disease, is up to 83% for stage IV and 70% for stage V d isease. Patients
with the much less common diffuse anap lastic Wilms' tumors have a much poorer
outcome, however. Their 4-year survival figures are 45% for stage III and only 7% for
stage IV disease.[20]
3.1.7 Clear cell sarcoma of the kidney
Clear cell sarcoma of the kidney (CCSK) is a distinct entity accounting for 4% of all
childhood renal neoplasms with a male preponderance. The peak age of inc idence is
similar to that of Wilms' tumor. There are no specific radiological features to help
distinguish CCSK from a Wilms' tumor. Although this neoplasm may metastas ise to
the lungs, there is a particular predilection for skeletal metastases at diagnosis (over
20% risk), hence the other known term, bone metastasizing tumor. Once diagnosed,
99mTc-MDP bone scintigraphy is ind icated for staging purposes. The discovery of a
lytic lesion in the skeleton in a child with a presumed diagnosis of Wilms' tumor
should suggest that the primary diagnosis is incorrect and that the tumor is likely to be
a CCSK, although ultimately d iagnosis rests on histo logical evaluation. Curiously,
although seen rarely at diagnosis, when relapse occurs with CCSK it seldom affects
the skeleton but more commonly relapses are seen in the lungs or central nervous
system.[32,6,7]
3.1.8 Rhabdoid tumor of the kidney
Rhabdoid tumor is the most aggressive malignant renal tumor in childhood and
accounts for about 1–2% of pediatric renal neoplasms. Most cases are diagnosed in
the first year of life (Fig .7). Like CCSK, the mass is indistinguishab le from a Wilms'
tumor on imaging. A peripheral fluid crescent sign on CT has been described but it is
not pathognomic and is seldom seen. Invasion of the renal vein is common.
Metastases to the lungs, liver and brain have been reported. There is also an
association with simultaneous primitive neuroectodermal tumors usually in the
posterior fossa. Consequently, cranial imaging is routinely rec ommended when this
renal tumor is encountered.[67]
Figure 7
Rhabdoid tumour. Axial T1W MRI post-gadolinium enhancement showing a large
heterogenous left renal mass with a hypointense metastasis in the right lo be of the
liver, due to metastatic rhabdoid tumor in an infant. This is usually a very aggressive
neoplasm. …[53]
3.1.9 Renal cell carcinoma
Renal cell carcinoma rarely presents in the first two decades of life. Less than 1% of
all cases occur in children. A mass or flank pain are common presenting features.
Haematuria is encountered less frequently. The mean age of presentation in childhood
is 9 years. A typ ically solid intrarenal mass cannot be distinguished from a Wilms'
tumor although ring-like calc ifications, unusual for a Wilms' tumor, may be present
within the mass. The major discriminating feature from a possible Wilms' tumor is the
older age of the patient. The frequency of this carcinoma in young patients may be
increasing, paralleling an increased incidence in adults. Locoregional nodal spread of
disease, in the absence of distal metastatic spread, does not appear to confer as poor a
prognosis in younger patients compared to adults. Metastases to the lungs, liver,
skeleton or brain are present in 20% of patients at diagnosis. [52]
3.1.10 Lymphoma and leukaemia
Renal invo lvement with or without retroperitoneal adenopathy is seen in 12% of
children with non-Hodgkin's lymphoma, most commonly B-cell Burkitt's lymphoma.
Multip le, usually bilateral, nodules are typ ical although diffuse infiltration may be
seen. There is generally widespread disease elsewhere. Renal enlargement on US with
altered echo texture is characteristic of both renal lymphoma and leukaemia. The
changes in the kidneys can be quite subtle on CT and are generally more conspicuous
on MRI, particularly T1W images after gadolinium enhancement. US is
recommended in all children with leukaemia/lymphoma prior to commencement of
chemotherapy to detect tumor infiltration or calyceal d ilatation. During initial
chemotherapy the excretion of tumor metabolites may result in renal obstruction or
uric acid nephropathy. Consequently children with leukaemic or lymphomatous
involvement of the kidneys need careful nephrological monitoring. [1]
3.2 liver tumors
Liver tumors overview
Tumors of the liver may be either malignant or benign. The liver is the third -most-
common site for intra-abdominal malignancy in children, following
adrenalneuroblastoma and Wilms tumor. The incidence of primary malignan liver
tumors per year is 1-1.5 per millio n children in the United States. This yields a
relative low rate for hepatic tumors (1.3% of all pediatric malignanc ies).Of hese
malignant tumors,hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the
most common and account for two thirds of all hepatic neoplasms. Benign liver
tumors inc ludehemangiomas, hamartomas, and focal nodular hyperp lasia (FNH).
Presentation and workup [70]
Most children with liver tumors present with abdominal d istension, a palpable
abdominal mass, or both. Anemia, thrombocytopenia, and leukocytosis are sometimes
present. Children with both HB and HCC may also present with weight loss, fever,
and anorexia.[66]
Fetal and neonatal presentations include hydramnios, fetal hydrops,congestive heart
failure and respiratory distress. Patients with congestive heart failure have been shown
to have lower survival rates. Cesarean delivery is recommended in cases when a
hepatic tumor is found using prenatal ultrasonography to prevent rupture.
Laboratory studies are performed to assess baseline CBC count, electrolyte levels,
liver enzyme levels, liver synthetic function, and α -fetoprotein (AFP) levels. AFP
levels are elevated in 50%-70% of children with hepatic neoplasms, and multip le
studies confirm that AFP is a valuab le surveillance marker in children who have
previous ly undergone hepatic resection for malignancy.[34]
The initial workup for hepatic masses includes rad iographic assessment using
ultrasonography to confirm the location and to characterize the consistency as cystic
or solid. Cystic or vascular lesions may not require any further imaging. CT scanning
and MRI (MRI) of the abdomen and chest are used for indeterminate or solid lesions
to further delineate the location, extent, and multip lic ity of the lesions and to detect
metastases. These modalities facilitate surgical planning and may determine
respectability; however, definitive diagnosis can be proven only through biopsy
findings.[28]
What are liver tumors?
Liver tumors are masses occurring in the liver that can be either benign or malignant
(cancerous). Tumors that are found at birth or early after delivery are often benign in
nature. While these require removal, no additional treatment with chemotherapy or
radiotherapy is required. One type of benign tumor is called mesenchymal
hamartoma. This tumor represents an abnormal collection of tissues seen in the
developing fetus, but not normally occurring in the liver. Surgical removal of the
tumor is the only treatment required. [51]
There are generally two types of rare malignant tumors and these require more
extens ive treatment. They are:
Hepatoblastoma
Hepatoblastoma is a cancerous liver tumor. The liver, the largest organ in the body,
consists of right and left lobes. (See Anatomy of the liver, below) The disease occurs
primarily in younger infants and children. With prompt treatment, hepatoblastoma is
remarkab ly responsive to chemotherapy. Hepatoblastoma cancer cells can spread
(metastasize) to other areas of the body. The most common sites of metastasis are the
lungs, abdomen and abdominal structures, and rarely to bone, the central nervous
system and bone marrow. [15]
Hepatocellular (liver carcinoma):
Hepatocellular carcinoma is a rare disease in which cancerous cells are found in the
tissues of the liver. This type of cancer is found in children from birth to 19 years of
age, but usually does not occur before the age of 15. The median age is 12 years old.
Hepatocellular carcinoma may occur in multiple sites within the liver, and is much
less responsive to chemotherapy than hepatoblastoma. Cancer cells can also spread
(metastasize) to other areas of the body. The most common sites of metastasis are the
lungs, into the abdomen and abdominal structures, and rarely to bone, the central
nervous system, and the bone marrow. [7]
Figure 8.
Ultrasound shows hyperechoic mass representing hepatocellular carcinoma.
Anatomy of the liver
The liver is located in the upper right-hand portion of the abdominal cavity, beneath
the diaphragm and on top of the stomach, right kidney, and intestines. Shaped like a
cone, the liver is a dark reddish-brown organ that weighs about three pounds. The
liver consists of two main lobes, both of which are made up of thousands of lobules.
These lobules are connected to small ducts that connect with larger ducts to ultimately
form the hepatic duct. The hepatic duct transports the bile prod uced by the liver cells
to the gallb ladder and duodenum (the first part of the small intestine). The liver
regulates most chemical levels in the b lood and excretes a product called "bile," which
helps carry away waste products from the liver.[68]
What causes liver tumors?
Although the exact cause of most liver tumors is unkn own, there are a number of
genetic conditions that are associated with an increased risk for developing childhood
liver cancers. Hepatoblastoma is associated with Beckwith -Wiedemann syndrome,
hemihypertrophy, and familial adenomatous polyposis.[62]
Other genetic conditions associated with liver cancers inc lude several inborn errors of
metabolism such as tyrosinemia, glycogen storage disease type 1, galactosemia, and
alpha-antitrypsin defic iency.[40]
Children who are exposed to hepatitis B infection at an early age or those who have
biliary artes ia are also at increased risk for developing liver cancer. Hepatocellular
carcinoma may arise in livers with an underlying abnormality such as familial
cholestatic cirrhosis, giant cell hepatitis of infancy, Fanconi's anemia, and glycogen
storage disease. Children who are exposed to hepatitis B or C infections at an early
age are at increased risk for developing hepatocellular carcinoma. Some
hepatocellular carcinomas and hepatoblastomas have genetic alterations in tumor
suppressor genes, which would explain the uncontrolled cell growth. [14]
What are the symptoms of liver tumors?
The following are the most common symptoms of liver tumors. However, each child
may experience symptoms differently. Symptoms may vary depending on the size of
the tumor, whether it is benign or malignant and if malignant, the presence and
location of metastases. Symptoms may inc lude:[64]
o a large abdominal mass, or swollen abdomen
o pain on the right side that may extend into the back and shoulder
o weight loss, decreased appetite
o abdominal pain
o vomiting
o jaund ice (yellowing of the eyes and skin)
o fever
o itching skin
o anemia (pale skin and lips from decreased number of red blood cells)
o back pain from compression of the tumor
How are liver tumors diagnosed?
In addition to a complete med ical history and physical examination, diagnostic
procedures for hepatocellular carcinoma may inc lude:
o biopsy – a sample of tissue removed from the tumo r and examined under a
microscope; the surgeon may also look at the liver us ing an instrument called a
laparoscope, a small tube with a light on the end
o complete blood count (CBC) – a measurement of size, number, and maturity of
different blood cells in a specific volume of blood
o additional blood tests – may inc lude blood chemistries, evaluation of liver and kidney
functions, and genetic studies
o multip le imaging studies, includ ing:
Computerized tomography scan (also called a CT or CAT scan) – a diagnostic
imaging procedure that uses a combination of x-rays and computer technology to
produce cross-sectional images (often called slices), both horizontally and vertically,
of the body. A CT scan shows detailed images of any part of the body, includ ing the
bones, muscles, fat, and organs. CT scans are more detailed than general x-rays.
magnetic resonance imaging (MRI) – a d iagnostic procedure that uses a combination
of large magnets, radiofrequencies, and a computer to produce detailed images of
organs and structures within the body
x-ray – a diagnostic test which uses invis ible electromagnetic energy beams to
produce images of internal tissues, bones, and organs onto film
Ultrasound (also called sonography) – a diagnostic imaging technique which uses
high-frequency sound waves and a computer to create images of blood vessels,
tissues, and organs. Ultrasounds are used to view internal organs as they function, and
to assess blood flow through various vessels.
Liver scans – pictures or x-rays taken of the liver after a dye has been injected that is
absorbed by liver tissue. These are used to detect tumors and liver abnormalities.
o alpha-fetoprotein (AFP) test – alpha-fetoprotein (AFP) levels in the blood can be used
to diagnose and follow response to treatment
What are the d ifferent stages of childhood liver cancer?
Staging is the process of determining whether cancer has spread and, if so, how far.
There are various staging symptoms that are used for hepatocellular carcinoma.
Always consult your child's physician for information on staging. One method of
staging is the following:[14]
o stage I – usually a tumor that can be completely removed with surgery
o stage II – usually a tumor that can mostly be removed by surgery but very small
amounts of the cancer are left in the liver
o stage III – usually a tumor that cannot be completely removed and the cancer cells are
found in the lymph nodes
o stage IV – cancer that has spread (metastasized) to other parts of the body
o Recurrent – the disease has returned after it has been treated. It may come back in the
liver or in another part of the body.
What are the treatments for liver tumors?
Specific treatment for hepatocellular carcinoma will be determined by your child's
physician based on:
o your child's age, overall health, and medical history
o extent of the disease
o your child's tolerance for specific medications, procedures, and therapies
o how your child's physician expects the disease to progress
o your opinion or preference
Treatment for benign tumors, such as mesenchymal hamartoma, requires surgical
removal of the tumor, and usually, no further therapy.
Treatments for liver cancers require c lose coordination between the pediatric surgeons
and pediatric oncologist who are managing your child's condition. Treatment for liver
cancer usually includes a combination of the following: [37]
o Surgery: Whether the tumor can be removed initially in treatment of hepatoblastoma
is a decision that must be made by the pediatric surgeon. If it is deemed that removal
would be extremely risky or pose a significant risk of leaving the tumor behind, then
the child may be treated initially with chemotherapy. After 3 or 4 courses of
treatment, surgical removal of the tumor is often much more read ily accomplished.
Surgery is the key treatment of children with hepatocellular carcinoma. Unfortunately,
successful removal of the tumor or tumors is difficult in children with hepatocellular
carcinoma for several reasons. One reason is that the disease may be present at
multip le sites within the liver. In addition, underlying cirrhosis or scarring within the
liver can make tumor removal much more difficult, and underlying metabolic
problems with the liver make normal liver function after surgery marginal.
o Chemotherapy – a drug treatment that works by interfering with the cancer cell's
ability to grow or reproduce. Different groups of drugs work in different ways to fight
cancer cells and shrink tumors. Chemotherapy may be used alone for some types of
cancer or in conjunction with other therapy such as radiation or surgery. Often, a
combination of chemotherapy drugs is used to fight a specific cancer. Certain
chemotherapy drugs may be given in a specific order depending on the type of cancer
it is being used to treat. While chemotherapy can be quite effective in treating certain
cancers, the agents do not differentiate normal healthy cells from cancer cells.
Because of this, there can be many adverse side effects during treatment. Being ab le
to anticipate these side effects can help the care team, parents, and child prepare, and,
in some cases, prevent these symptoms from occurring, if possible. Chemotherapy is
systemic treatment, meaning it is introduced to the bloodstream and travels
throughout the body to kill cancer cells. Chemotherapy can be given: [62]
as a pill to swallow
as an injection into the muscle or fat tissue
intravenously (directly to the bloodstream; also called IV)
intrathecally – chemotherapy given directly into the spinal column with a needle
o radiation therapy – using high-energy rays (radiation) from a specialized machine to
damage or kill cancer cells and shrink tumors
o Liver transplant – the liver of the child affected with liver cancer may be replaced with
a liver from a donor, although this is rare. (See Liver Transplantation.) Your child's
physician will provide more information on whether this is an option for your child
and the process involved. [4,21]
o supportive care – any type of treatment to prevent and treat infections, side effects of
treatments, and complications, and to keep your child comfortable during treatment
o Continuous follow-up care – a schedule of follow-up care determined by your child's
physician and other members of your care team to monitor ongoing response to
treatment and possible late effects of treatment. [4]
What is the long-term outlook for patients with liver tumors?
Children who have had a benign tumor removed usually have no further problems.
Children with hepatoblastoma can often be cured. Studies have shown that after the
cancerous tumor is removed, along with the removal of a major segment of the liver,
the liver has a remarkab le capacity to regenerate or grow towards the normal vo lume
that it had prior to removal. Long-term follow-up studies of children have shown that
the liver continues to grow and often remains very close to what would be the
predicted normal s ize of the liver despite removal of up to two -thirds of the liver
during infancy. Long-term insufficiency of the liver is rarely seen except in those
children who have the significant metabolic abnormalities associated with
hepatocellular carcinoma. These children would require liver transplantation. [70]
As with any cancer, prognosis and long-term survival can vary greatly from child to
child. Prompt medical attention and aggressive therapy are important for the best
prognosis. Continuous follow-up care is essential for a child diagnosed with a liver
cancer. New methods are continually being discovered to improve treatment and to
decrease side effects.[32]
What is the latest research on liver cancer?
Children's Hospital and Dana-Farber Cancer Institute are conducting numerous
research studies that will help clinicians better understand and treat liver cancers.
Other types of treatment currently being studied inc lude:[9]
o Biological therap ies – a wide range of substances that may be able to invo lve the
bodies own immune system to fight cancer or lessen harmful s ide effects of some
treatments.
o New ways of delivering chemotherapy – researchers are studying new delivery
strategies, such as putting chemotherapy directly into the liver.
o Cryotherapy – surgeons are studying new ways of using this existing treatment, which
uses extreme cold to destroy unwanted tissue) for liver cancer.
3.3 Pancreatic tumors
Pancreatic tumors can be of either endocrine or nonendocrine origin. Tumors of
endocrine origin inc lude insulinomas and gastrinomas. These and other functioning
tumors occur in the autosomal dominantly inherited multip le endocrine neoplas ia type
1 (MEN-1). Hypoglycemia accompanied by higher than expected insulin levels or
refractory gastric ulcers (Zollinger-Ellison syndrome) ind icate the possibility of a
pancreatic tumor .Most gastrinomas arise outside of the pancreas. The treatment of
choice is surgical removal. If the primary tumor cannot be found or if it has
metastasized, cure might not be possible. Treatment with high dose of a proton pump
inhib itor to inhib it gastric acid secretion is then ind icated. [23]
Figure 9.
CT scan image with oral and intravenous contrast in a patient with biochemical
evidence of insulinoma. The 3-cm contrast-enhancing neoplasm (arrow) is seen in the
tail of the pancreas (P) posterior to the stomach[46]
The watery diarrhea-hypokalemia-acidosis syndrome is usually produced by the
secretion of vasoactive intestinal peptide (VIP) by a non–α-cell tumor (VIPoma) (see
Table 333-7). VIP levels are often, but not always, increased in the serum. Treatment
is surgical removal of the tumor. When this is not possible, symptoms may be
controlled by the use of octreotide acetate (cyclic somatostatin, Sandostatin), a
synthetic analog of somatostatin. Pancreatic tumors secreting a variety of hormones,
includ ing glucagon, somatostatin, and pancreatic polypeptide have also been
described. The treatment is surgical resection when possible. Pancreatoblastomas,
pancreatic adenocarcinomas, cystadenomas, and rhabdomyosarcomas are rarely
encountered. Pancreatoblastoma, a malignant embryonal tumor that secretes α-
fetoprotein and can contain both endocrine and exocrine elements, is the most
common pancreatic neoplasm in young children. Presurgical chemotherapy should be
considered for lesions not primarily respectable. Resection can be curative; adjuvant
chemotherapy has been used but its effectiveness is not established. Carcinoma of the
exocrine pancreas is a major problem in adults, accounting for 2% of diagnoses and
5% of deaths due to cancer. It is very rare in childhood. No definite causes are known.
Several genetic syndromes including mutations in the PRSS1 and MEN-1 genes lead
to an increased inc idence of pancreatic cancer in adult life. The Frantz tumor is a
papillary cystic tumor usually found in girls and young women. Typical presenting
symptoms are abdominal pain, mass, or jaund ice. The treatment of choice is total
surgical removal.[17]
Insulinomas and persistent hyperinsulinemic hypoglycemia of infancy produce
symptomatic hypoglycemia most commonly caused by mutations in the ABCC8 gene.
Massive subtotal or total pancreatectomy is the treatment of choice when medical
treatment fails . These children might then develop pancreatic insuffic iency and
diabetes as a complication of surgery. Pancreatic les ions in von Hippel-Lindau d isease
are usually benign and cystic. Cystadenomas, familial adenocarcinomas, and islet cell
tumors are less common. Metastases have been reported, but adjuvant therapy after
surgical excision cannot yet be recommended. The d iagnosis is suggested by CT
scanning. Prognosis is good for completely resected endocrine tumors but very poor
for carcinomas, even with extens ive surgery. Children who survive partial or complete
pancreatectomy may have decreased pancreatic exocrine and endocrine reserve.[7]
3.4 Gastrointestinal Stromal
Tumors Epidemio logy
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors whose
classification is hindered by anecdotal reports, failure to distinguish between p rimary
and secondary GISTs, and the mixing of benign and malignant tumors in the reports.
In addition, GISTs arising from various anatomic sites have been reported together,
making prediction of their clinical behavior difficult. The most common site is the
44
stomach (50% to 70%), followed by the small intestine (20% to 30%), colon or
rectum (10%), and esophagus (5%).[29]
Figure 10.
malignant gastric GIST. Axial unenhanced CT image shows a well-defined exophtic-
growth homogeneous mass (arrow) with hemorrhage (arrowhead) of the stomach
CLINICAL PRESENTATION
Patients with GIST tumors present with nonspecific symptoms, often generalized
abdominal pain, dyspepsia, and occult GI bleed ing. Iron-defic iency anemia should
prompt an investigation to exclude a GI tract malignancy as the cause.1 Less
commonly, patients present with a palp able abdominal mass or intestinal obstruction.
Standard imaging studies may assist in the d iagnosis (plain radiographs and computed
tomography [CT]). Endoscopy can identify a tumor mass in the stomach, duodenum,
or colon.[43]
PATHOLOGY
GISTs are classified as mesenchymal tumors of the GI tract thought to originate from
the intestinal cell of Cajal, an intestinal pacemaker cell. Historically, smooth muscle
tumors, such as leiomyomas and leiomyosarcomas, and neural tumors, such as nerve
sheath tumors, have been categorized as GISTs. GISTs are now defined as cellular
spindle cell, epithelio id, or occasional pleomorphic mesenchymal tumors that express
the KIT (CD117, stem cell factor receptor) protein, as detected by
immunohistochemistry. Additional cell type markers, such as CD34, smooth muscle
actin, desmin, and S-100 protein, are also used to establish a diagnosis of GIST. These
histologic and immunohistochemical features now distinguis h GISTs from
leio myomas, leiomyosarcomas, neural tumors, and other tumors of smooth muscle
origin. Prognosis relies on traditional pathologic staging criteria, such as size, extent
of tumor invasion into mucosa or surrounding organs, mitotic index, and nuc lear
pleomorphism. However, no single feature is consistently reliab le in pred icting
outcome.[10]
Determining prognosis of pediatric patients with GIST tumors can be controversial.
The usual criteria for assessing risk of malignancy (i.e., tumor size, mitotic activity,
anatomic location) are not reliab le in pediatric GIST. Children frequently present with
multip le gastric nodules, making identification of a dominant mass difficult.
Secondly, there exists a wide variation in proliferation index between patients and
even among multip le tumors within the same patient. Furthermore, some pediatric
patients develop GIST metastasis despite being classified as low risk by adult criteria,
and others with low proliferation ind ices develop recurrent disease in perigastric nodal
basins, the peritoneum, or liver. Pediatric GIST is distinguished as a separate clinical,
pathologic, and molecular subset with a predisposition for females, multifocal gas tric
tumors, and wild-type KIT/PDGRA genotype. This is in contrast to older-age, adult
GIST and even GIST in young adults. All these factors must be considered when
distinguishing benign from malignant pediatric gastric stromal tumors. [42]
TREATMENT
Complete surgical excis ion of GISTs, along with the pseudocapsule, is the treatment
of choice. Achieving negative pathologic margins is frequently possible, because
GISTs tend to hang from and do not diffusely infiltrate the structure from which they
arise. Consequently, wedge resection of the stomach or segmental resection of the
intestine provides adequate therapy; wide resection is not necessary. In addition,
because the status of microscopic margins does not appear to be important for
survival, vital structures should not be sacrificed if gross tumor clearance has been
attained. GIST rarely metastasizes to lymph nodes; so, lymphadenectomy is seldom
warranted.[11]
The high rate of local and distant recurrence underscores the need for adjuvant
therapy. GIST has traditionally been resistant to radiotherapy; however, imatinib
mesylate, a selective KIT, PDGF-RA, PDGR-RB, and BCR-ABL tyrosine kinase
inhib itor, has been successful as a first-line agent in treating advanced and metastatic
GIST in adult patients. Imatinib blocks the constitutive activity of KIT receptor in
GIST cells. Recently, a mutation in the c -KIT gene on exon-11 associated with
increased risk of recurrence and higher mortality was identified. The efficacy of
imatinib is related to GIST genotype, with KIT exon-11–mutated GISTs being more
sensitive to imatinib than wild-type (WT) tumors. While imatinib mesylate has been
effective ad juvant therapy for adult GISTs, pediatric GIST lesions are frequently less
responsive. The lack of efficacy may result from pediatric GISTs being predominantly
WT genotype and lacking the KIT mutations more commonly detected in adult GIST
tumors. Secondgeneration kinase inhib itors (i.e., sunitinib, nilotinib, sorafenib, and
dasatinib) have demonstrated in vivo and in vitro efficacy in treatment of malignancy
with KIT mutations. Although investigations of adjuvant and neoadjuvant tyrosine
kinase inhibitors are ongoing, surgical exc is ion remains the initial option for pediatric
GISTs. Adjuvant chemotherapy with imatinib and other agents may be used in cases
of incomplete resection, tumor spillage, or other high-risk factors. For recurrent or
metastatic GIST, a trial of a kinase inhib itor, followed by surgical resection, may be
effective. Neoadjuvant tyrosine kinase inhib itor chemotherapy may similarly reduce
unresectable GIST lesions making surgical resection possib le. These therapies may
decrease the inc idence of postoperative GIST recurrence and spread, and thereby
extend survival. [33]
Intestinal Tumors
3.4.1 Myofibromatosis
Infantile myofibromatosis is a mesenchymal tumor that can arise in the skin, muscle,
bone, subcutaneous tissue, or viscera. It is the most common fibrous tumor of infancy.
Myofibromatosis presents with either solitary or generalized lesions, with or without
visceral involvement. Most les ions spontaneously regress; however, extensive
intestinal myofibromatosis is associated with significant morbidity and mortality.
Various chemotherapeutic interventions have demonstrated limited efficacy,
significant treatment toxicity, and long-term morbid ity. However, the combination of
lowdose chemotherapy and long-term total parental nutrition for life-threatening
infantile myofibromatosis can provide symptomatic relief and inhib it d isease
progression.[37]
3.4.2 Lymphoma
Lymphoma is the most common small bowel malignancy in children, with high -grade
non-Hodgkin lymphoma 74% of these tumors. Burkitt lymphoma constitutes the
comprising most common histologic subtype. The majority of patients (50% to 93%)
present with lymphoma localized to the distal small bowel, although tumor may occur
anywhere from the stomach to the rectum. Patients may present with chronic GI
distress, occult blood per rectum, hematochezia, and/or an abdominal mass. An acute
worsening of symptoms may result in emergency surgery for treatment of ileocolic
intussusception, with lymphoma creating the lead point (46%), acute appendicitis
(22%), perforation (11%), or obstruction (8%). Higher mortality is associated with
advanced disease stage, intestinal perforation, high-grade histo logy, and T-cell
lymphomas.[22]
Surgical management depends on disease presentatio n, as well as extent of disease at
presentation. Bulky disease is usually not completely resectable. Extens ive resection
of bulky retroperitoneal or mesenteric disease does not enhance survival; nevertheless,
complete surgical resection (including bowel resection), if possible, significantly
enhances the prognosis of patients with intestinal lymphoma, especially when
included in a multimodality treatment approach. Tumor downstaging by complete
resection allows for decreased duration and intensity of post-operative chemotherapy.
When operating for a complication of intraperitoneal disease, the extent of the
procedure should be limited to resolution of the complication and resection of
suffic ient tissue to ensure an accurate d iagnosis. If limited disease is encountered,
complete resection and an evaluation of mesenteric, perihepatic, and periaortic nodes
should be undertaken to assess for regional metastatic spread. Two -year cumulative
survival for intestinal B-cell lymphoma is 94% and 28% for intestinal T -cell
lymphoma. The overall 5- and 10-year survival rates for all intestinal lymphoma
patients treated with multimodality therapy (surgery, rad iation, chemotherapy) are
52% and 44%, respectively. The corresponding disease-free survival rates are 43%
and 38%, respectively.[53]
3.4.3Carcinoid Tumors
EPIDEMI OLOGY
Carcinoid tumors originate from neuroendocrine cells within the GI tract. These
neoplasms derive from GI epithelial and subepithelial endocrine progenitor cells that
function as part of the amine precursor uptake and decarboxylation (APUD) system.
Carcinoids can also be found in the lungs, mediastinum, thymus, liver, pancreas,
bronchus, ovaries, prostate, testes, and kidneys. Pediatric carcino id tumors typically
occur in the GI tract—stomach, small intestine, appendix (most common), and
rectum. Carcino id tumors of the appendix occur with an estimated incidence of 1 case
per million children per year, with a slight female predominance[69]
DIAGNOSIS
Carcinoid tumors are classified according to the location of origin in the primitive gut
(foregut, midgut, and hindgut). Foregut tumors include carcinoids of the lung,
bronchus, stomach, proximal duodenum, and pancreas. Midgut tumors arise from the
distal duodenum, jejunum, ileum, and right colon, inc lud ing the appendix. These
account for 60% to 80% of all carcino ids in adults and children. Hindgut tumors arise
in the transverse and distal colon and rectum. Tumors can also arise from a Meckel
diverticulum, enteric duplications, and the mesentery. Appendiceal carcinoids are the
most common, with more than 70% of these tumors developing at the appendiceal tip.
Pediatric carcino id tumors are often d iscovered incidentally during an operation for
presumed appendicitis or another unrelated diagnosis. Although appendicitis or
another unrelated diagnosis. Although clinical signs of acute appendicitis or
gynecologic pathology may prompt exploration, true inflammatory changes of acute
appendicitis are not often induced by the carcinoid, possibly because of the distal
location of the tumor and absence of proximal luminal obstruction. The most serious
complication of carcinoid tumors is a carcino id crisis,which ismost often associated
with foregut tumors, larger tumors, and high serum/urine 5-hydroxyindoleacetic acid
(5-HIAA) levels. Although pediatric carcino ids vary in size, carcinoid syndrome
(flushing, diarrhea, abdominal pain, tachycard ia, hypertension, hypotension, altered
mental status, and coma) has not been typica lly associated with tumors confined to the
appendix. In contrast, pediatric patients with extra -appendiceal carcino id tumors, such
as in the lung or liver, are often symptomatic. Biologically active amines (serotonin,
catecholamines, histamine) and metabolites (5-HIAA) are characteristically elevated
in the plasma and urine of patients with symptomatic carcinoid tumors. Patients with
extra-appendiceal carcino ids frequently present with disseminated disease at the time
of diagnosis and have a higher inc idence of recurrent tumor following the initial
diagnosis and resection.[11,54]
TREATMENT
Tumor size at presentation dictates surgical decision making for carcinoid tumors of
the appendix. For appendiceal carcinoid tumors less than 2 cm in diameter, surgical
resection of the appendix and mesoappendix is considered curative. Long-term
follow-up demonstrates minimal d isease recurrence and a rare likelihood of metastatic
disease. Carcinoid tumors greater than 2 cm, those with cecal involvement, lymphatic
invas ion, lymph node invo lvement, mesoappendix infiltration, positive resection
margins, goblet cell malignancy, or cellular pleomorphism with a high mitotic index
require a more extens ive resection (i.e., a right hemicolectomy with associated
resection of the mesocolon).[17]
3.4.4 Colorectal Adenocarcinoma
Adenocarcinoma of the colon and rectum is the most common cancer of the GI tract,
with approximately 142,570 new cases and 51,370 deaths in the United Sates in the
past year. The lifetime risk of developing colorectal cancer in the general population
is 1 in 19. However, colorectal cancer in children is rare, with an estimated incidence
of 0.3 to 1.5 cases per millio n. Although reported as early as 9 months of age, the
median age at diagnosis for pediatric cases is 15 to 19 years. Pediatric colorectal
cancer accounts for 2% of malignancies in adolescents. Colorectal cancer d iffers
greatly between adults and children. These differences include the presenting signs
and symptoms, primary site of the tumor, pathologic find ings, stage, and prognosis.
Carcinoma of the colon is associated with several predisposing factors, including
ionizing rad iation (e.g., CT scan, therapeutic radiatio n treatments), polyposis
syndromes, urinary divers ion with previous ureterosigmo idostomy, and chronic
parasitic infection. Various environmental factors, includ ing herb icide exposure, may
also be associated with tumor formation.[48]
Figure 11.
Patient undergo ing staging for adenocarcinoma of the descending colon. Axial scan
demonstrates circumferential wall thickening and invas ion into pericecal mesentery.
CHAP TER 4 : CASE HISTORY
Baby C., aged 11, was admitted urgently to the general surgery department in the
Centre of National Scientific and Practical Center of Pediatric Surgery "Academic ian
Natalia Gheorghiu" IMșiC with c linically suspected acute abdomen
From history it is known that the child is ill for a two weeks, and they come with
symptoms of nausea, vomiting and periodic abdominal pain. The dynamics of
abdominal pain worsened, there were cold sweats during sleep and exercise
insignificant, dyspnea.
On physical examination was reveal :
Oval and distended abdomen, , excess adipose tissue developed without defans
muscle, soft to touch, pain in the epigastric and left flank.
Negative peritoneal sign.
Gaz emits.
Lung ascultation : harsh breathing s ound , subdued on the lower left.
Laboratory analysis:
Blood group B(III), Rh (+)
Hemoglobin 129 g/l
RBC’s 4.5
Ht 0.9
WBC’s 12.2
Nonsegmented neutrophils 6
Segmented neutrophils 63
Eosinophils 1
lymphocytes 22
Monocytes 8
ESR 16
Platelets 585
Total protein 58 g/l
Urea 3.6
Creatinine 0.056
Bilirubin 7
K+ 3.16
Na 125
ALT 27
AST 35
Prothrombin 89%
Fibrinogen 2.44
Glucose 4.5
Sample Thymo l 4.9
Cholesterol 3.75
Alkaline phosphatase 114
56
Paraclinical Investigation:
Chest X-RAY:
Indicates the opacity on the left supradiafragmal and left sinus
CONCLUSION: pneumonia complicated by pleural effusion on the left
ultrasound of the abdomen
dilatation of intestinal loops in abdomen
Between intestines than free liquid
Appendix wall thickened to 3.2 mm
Under the left costal margin determining a tumor 6-8cm
Computed tomography of the abdomen
Formation volume projection proximal jejunum dimens ions 74×56 x78mm,
heterogeneous structure
Tumor formation over significant expansion intestines
In the omentum (vo iced at the bottom) is determined diffuse stromal proliferative
process in the hepatic hilum and the crack intralobare – multip le formations
multiboselate accounts
Intraoperative
After preoperative preparation superior med ian laparotomy was performed under
endotracheal anesthes ia.
On opening the peritoneal cavity was removed about 1000 ml liquid turb id, thick
color-bleeding Suri. To review multip le abdominal organs to detect nodular tumor
formation.
Throughout the omentum with nodular tumor formations hard-elastic consistency,
different sizes.
Omentectomy was carried out total
Meso thickened bowel with lymph nodes enlarge
Ileojejunală region was found a tumor in a process invaginated jejunum size 11x
6cm., Hard consistency, bowel wall involved in the process of blood stasis, swelling.
Attempt was made without success dezinvaginare.
Supraadiacent advanced dilated bowel. Intussusception was performed with resection
anastomosis latero laterale application.
From the left pleural cavity was removed a liter of fluid disorders and installed
intercostal drain connected to the Bulau.
Histological Examinatio
the diagnosis – non-Hodgkin's lymphoma affecting meso form and the adjacent bowel,
omentum.
In our experience two positions are outlined below which have tumors in children.
The first position is represent diagnostic difficulties, differential diagnosis of tumors in children. At an
early diagnosis surgery, the adjuvant can not even solve neglijiab ilă mortality.
The second position in which the tumor forms are in the late diagnosis, when the surgical instrument is
associated with metastasis is a true nightmare for the operator and results in an alteration in the biological
progressively s lower or faster but often fatal completed.
68
CHAP TER 5:CONCLUSION
Advances in mo lecular genetics research in the past 3 decades have led to an
increased understanding of the genetic events in the pathogenesis and progression of
human malignanc ies, including those of childhood. A number of pediatric
malignanc ies serve as models for the molecular genetics approach to cancer.
The pediatric experience highlights the utility of molecular analys is for a variety of
purposes. Demonstration of tumorspecific trans locations by cytogenetics, FISH, and
RT-PCR confirms histopathologic diagnoses. Detection of chromosomal
abnormalities, gene overexpression, and gene amplification is used in risk
stratification and treatment planning. Elucidation of pathways invo lving tumor
suppressor genes has increased our understand ing of syndromes associated with
cancer and has led the way for genetic screening and counseling and prophylactic
surgical intervention. And in the near future, translation of the mo lecular profile of a
given tumor will form the basis of a new therapeutic approach. Treatment will be
tailored such that patients with biologically high-risk tumors receive intensified
regimens to achieve a cure, whereas patients with bio logically low-risk tumors may
experience a cure and benefit from the lower toxic ity of nonintens ive therapy.
Elucidation of the complex molecular pathways invo lved in tumorigenesis will also
encourage the production of targeted anticancer agents with high specificity, effic acy,
and therapeutic index.
69
References
1. Ribeiro RC, Figueiredo B: Childhood adrenocortical tumours. Eur J Cancer 40 (8):
1117-26, 2004.
2. Wooten MD, King DK: Adrenal cortical carcinoma. Epidemio logy and treatment
with mitotane and a review of the literature. Cancer 72 (11): 3145-55, 1993 .
3. Michalkiewicz E, Sandrini R, Figueiredo B, et al. : C linical and outcome
characteristics of children with adrenocortical tumors: a report from the
International Pediatric Adrenocortical Tumor Registry. J Clin Oncol 22 (5): 838-
45, 2004 .
4. Berstein L, Gurney JG : Carcinomas and other malignant ep ithelial neoplasms. In:
Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer inc idence and survival among
children and adolescents: United States SEER Program 1975-1995. Bethesda, Md:
National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649 ., Chapter
11, pp 139-148. Also availab le online. Last accessed January 29, 2014.
5. Figueiredo BC, Sandrini R, Zambetti GP, et al. : Penetrance of adrenocortical
tumours associated with the germline TP53 R337H mutation. J Med G enet 43 (1):
91-6, 2006.
6. Pianovski MA, Maluf EM, de Carvalho DS, et al. : Mortality rate of adrenocortical
tumors in children under 15 years of age in Curitiba, Brazil. Pediatr Blood Cancer
47 (1): 56-60, 2006 .
7. Rodriguez-Galindo C, Figueiredo BC, Zambetti GP, et al. : Bio logy, clinical
characteristics, and management of adrenocortical tumors in children. Pediatr
70 Blood Cancer 45 (3): 265-73, 2005 .
8. Ribeiro RC, Sandrini Neto RS, Schell MJ, et al. : Adrenocortical carcinoma in
children: a study of 40 cases. J Clin Oncol 8 (1): 67-74, 1990. [PUBMED
Abstract]
9. Wieneke JA, Thompson LD, Heffess CS: Adrenal cortical neoplasms in the
pediatric population: a clinicopathologic and immunophenotypic analysis of 83
patients. Am J Surg Pathol 27 (7): 867-81, 2003.
10.Sandrini R, Ribeiro RC, DeLacerda L: Childhood adrenocortical tumors. J Clin
Endocrinol Metab 82 (7): 2027-31, 1997
11.Bugg MF, Ribeiro RC, Roberson PK, et al. : Correlation of pathologic features
with clinical outcome in pediatric adrenocortical neoplasia. A study of a
Brazilian population. Brazilian Group for Treatment of Childhood
Adrenocortical Tumors. Am J Clin Pathol 101 (5): 625 -9, 1994.
12.Redlich A, Boxberger N, Strugala D, et al. : Systemic treatment of
adrenocortical carcinoma in children: data from the German GPOH-MET 97
trial. Klin Padiatr 224 (6): 366-71, 2012.
13.Michalkiewicz EL, Sandrini R, Bugg MF, et al. : Clinical characteristics of
small functioning adrenocortical tumors in children. Med Pediatr Oncol 28
(3): 175-8, 1997.
14.Ribeiro RC, Sandrini F, Figueiredo B, et al. : An inherited p53 mutation that
contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma.
Proc Natl Acad Sci U S A 98 (16): 9330-5, 2001.
15.Custódio G, Parise GA, Kiesel Filho N, et al. : Impact of neonatal screening
71 and surveillance for the TP53 R337H mutation on early detection of
childhood adrenocortical tumors. J Clin Oncol 31 (20): 2619-26, 2013 .
16.Hoyme HE, Seaver LH, Jones KL, et al. : Isolated hemihyperplasia
(hemihypertrophy): report of a prospective multicenter study of the inc idence
of neoplasia and review. Am J Med Genet 79 (4): 274-8, 1998 .
17.Wijnen M, Alders M, Zwaan CM, et al. : KCNQ1OT1 hypomethylation: a novel
disguised genetic predisposition in sporadic pediatric adrenocortical tumors?
Pediatr Blood Cancer 59 (3): 565-6, 2012.
18.Steenman M, Westerveld A, Mannens M: Genetics of Beckwith-Wiedemann
syndrome-associated tumors: common genetic pathways. Genes Chromosomes
Cancer 28 (1): 1-13, 2000 .
19.El Wakil A, Doghman M, Latre De Late P, et al. : Genetics and genomics of
childhood adrenocortical tumors. Mol Cell Endocrino l 336 (1-2): 169-73, 2011.
20.Figueiredo BC, Stratakis CA, Sandrini R, et al. : Comparative genomic
hybrid ization analys is of adrenocortical tumors of childhood. J Clin Endocrinol
Metab 84 (3): 1116-21, 1999 .
21.Weiss LM: Comparative histologic study of 43 metastasizing and
nonmetastas izing adrenocortical tumors. Am J Surg Pathol 8 (3): 163-9, 1984.
22.van S looten H, Schaberg A, Smeenk D, et al. : Morphologic characteristics of
benign and malignant adrenocortical tumors. Cancer 55 (4): 766-73, 1985 .
23.Stojadinovic A, Ghossein RA, Hoos A, et al. : Adrenocortical carcinoma:
clinical, morphologic, and molecular characterization. J Clin Oncol 20 (4): 941-
50, 2002 .
24.Almeida MQ, Fragoso MC, Lotfi CF, et al. : Expression of insulin-like growth
72 factor-II and its receptor in pediatric and adult adrenocortical tumors. J Clin
Endocrinol Metab 93 (9): 3524-31, 2008.
16.Hoyme HE, Seaver LH, Jones KL, et al. : Isolated hemihyperplasia
(hemihypertrophy): report of a prospective multicenter study of the inc idence
of neoplasia and review. Am J Med Genet 79 (4): 274-8, 1998 .
17.Wijnen M, Alders M, Zwaan CM, et al. : KCNQ1OT1 hypomethylation: a novel
disguised genetic predisposition in sporadic pediatric adrenocortical tumors?
Pediatr Blood Cancer 59 (3): 565-6, 2012.
18.Steenman M, Westerveld A, Mannens M: Genetics of Beckwith-Wiedemann
syndrome-associated tumors: common genetic pathways. Genes Chromosomes
Cancer 28 (1): 1-13, 2000 .
19.El Wakil A, Doghman M, Latre De Late P, et al. : Genetics and genomics of
childhood adrenocortical tumors. Mol Cell Endocrino l 336 (1-2): 169-73, 2011.
20.Figueiredo BC, Stratakis CA, Sandrini R, et al. : Comparative genomic
hybrid ization analys is of adrenocortical tumors of childhood. J Clin Endocrinol
Metab 84 (3): 1116-21, 1999 .
21.Weiss LM: Comparative histologic study of 43 metastasizing and
nonmetastas izing adrenocortical tumors. Am J Surg Pathol 8 (3): 163-9, 1984.
22.van S looten H, Schaberg A, Smeenk D, et al. : Morphologic characteristics of
benign and malignant adrenocortical tumors. Cancer 55 (4): 766-73, 1985 .
23.Stojadinovic A, Ghossein RA, Hoos A, et al. : Adrenocortical carcinoma:
clinical, morphologic, and molecular characterization. J Clin Oncol 20 (4): 941-
50, 2002 .
24.Almeida MQ, Fragoso MC, Lotfi CF, et al. : Expression of insulin-like growth
73 factor-II and its receptor in pediatric and adult adrenocortical tumors. J Clin
Endocrinol Metab 93 (9): 3524-31, 2008.
25.West AN, Neale GA, Pounds S, et al.: Gene expression profiling of childhood
adrenocortical tumors. Cancer Res 67 (2): 600-8, 2007.
26.Ghazi AA, Mofid D, Salehian MT, et al. : Functioning adrenocortical tumors in
children-secretory behavior. J Clin Res Pediatr Endocrinol 5 (1): 27-32, 2013.
27.Hanna AM, Pham TH, Askegard-Giesmann JR, et al. : Outcome of adrenocortical
tumors in children. J Pediatr Surg 43 (5): 843-9, 2008.
28.Klein JD, Turner CG, Gray FL, et al.: Adrenal cortical tumors in children: factors
associated with poor outcome. J Pediatr Surg 46 (6): 1201-7, 2011.
29.Zancanella P, Pianovski MA, Oliveira BH, et al. : Mitotane associated with
cisplatin, etoposide, and doxorubicin in advanced childhood adrenocortical
carcinoma: mitotane monitoring and tumor regression. J Pediatr Hematol Oncol 28
(8): 513-24, 2006 .
30.Hovi L, Wikström S, Vettenranta K, et al. : Adrenocortical carcinoma in children: a
role for etoposide and cisplatin ad juvant therapy? Preliminary report. Med Pediatr
Oncol 40 (5): 324-6, 2003.
31.Stewart JN, Flageo le H, Kavan P : A surgical approach to adrenocortical tumors in
children: the mainstay of treatment. J Pediatr Surg 39 (5): 759-63, 2004.
32.Hubertus J, Boxberger N, Redlich A, et al. : Surgical aspects in the treatment of
adrenocortical carcinomas in children: data of the GPOH-MET 97 trial. Klin
Padiatr 224 (3): 143-7, 2012.
33.Kardar AH: Rupture of adrenal carcinoma after biopsy. J Urol 166 (3): 984, 2001.
74 34.Gonzalez RJ, Shapiro S, Sarlis N, et al. : Laparoscopic resection of adrenal cortical
carcinoma: a cautionary note. Surgery 138 (6): 1078-85; discussion 1085-6, 2005.
35.Terzolo M, Angeli A, Fassnacht M, et al. : Adjuvant mitotane treatment for
adrenocortical carcinoma. N Engl J Med 356 (23): 2372-80, 2007.
36.Driver CP, Birch J, Gough DC, et al. : Adrenal cortical tumors in childhood.
Pediatr Hemato l Oncol 15 (6): 527-32, 1998 Nov-Dec.
37.Curtis JL, Burns RC, Wang L, et al. : Primary gastric tumors of infancy and
childhood: 54-year experience at a single institution. J Pediatr Surg 43 (8):
1487-93, 2008.
38.Subbiah V, Varadhachary G, Herzog CE, et al. : Gastric adenocarcinoma in
children and adolescents. Pediatr Blood Cancer 57 (3): 524 -7, 2011.
39.American Cancer Society. : Cancer Facts and Figures-2000. Atlanta, Ga:
American Cancer Society, 2000.
40.Rowland M, Drumm B: Helicobacter pylori infection and peptic ulcer d isease
in children. Curr Opin Pediatr 7 (5): 553-9, 1995.
41.Ajani JA: Current status of therapy for advanced gastric carcinoma. Oncology
(Huntingt) 12 (8 Suppl 6): 99-102, 1998 .
42.Chung EM, Travis MD, Conran R M: Pancreatic tumors in children: radio logic –
pathologic correlation. Radiographics 26 (4): 1211-38, 2006 Jul-Aug.
43.Perez EA, Gutierrez JC, Koniaris LG, et al. : Malignant pancreatic tumors:
incidence and outcome in 58 pediatric patients. J Pediatr Surg 44 (1): 197 -203,
2009.
44.Dall' igna P, Cecchetto G, Bisogno G, et al. : Pancreatic tumors in children and
75 adolescents: the Italian TREP project experience. Pediatr Blood Cancer 54 (5):
675-80, 2010
45.Brecht IB, Schneider DT, Klöppel G, et al. : Malignant pancreatic tumors in
children and young adults: evaluation of 228 patients identified through the
Surveillance, Epidemio logy, and End Result (SEER) database. Klin Padiatr 223
(6): 341-5, 2011.
46.Vossen S, Goretzki PE, Goebel U, et al. : Therapeutic management of rare
malignant pancreatic tumors in children. World J Surg 22 (8): 879-82, 1998.
47.Shorter NA, G lick RD, Klimstra DS, et al. : Malignant pancreatic tumors in
childhood and adolescence: The Memorial S loan-Kettering experience, 1967 to
present. J Pediatr Surg 37 (6): 887-92, 2002.
48.Raffel A, Cupisti K, Krausch M, et al. : Therapeutic strategy of papillary cystic
and solid neoplasm (PCSN): a rare non-endocrine tumor of the pancreas in
children. Surg Oncol 13 (1): 1-6, 2004 .
49.Ellerkamp V, Warmann SW, Vorwerk P, et al. : Exocrine pancreatic tumors in
childhood in Germany. Pediatr Blood Cancer 58 (3): 366-71, 2012 .
50.van den Akker M, Angelini P, Taylor G, et al.: Malignant pancreatic tumors in
children: a single-institution series. J Pediatr Surg 47 (4): 681-7, 2012.
51.Movahedi-Lankarani S, Hruban RH, Westra WH, et al. : Primitive
neuroectodermal tumors of the pancreas: a report of seven cases of a rare
neoplasm. Am J Surg Pathol 26 (8): 1040-7, 2002 .
52. Rha SE, Byun JY, Jung SE, Chun HJ, Lee HG, Lee JM. Neurogenic tumors in
the abdomen: tumor types and imaging characteristics. Radiographics.
2003;23:29–43.
76
53 Evans AE, d'Angio GJ, Propert K, et al. Prognostic factors in neuroblastoma.
Cancer. 1987 ;59:1853–9.
54. Rubie H, Hartmann O, Michon J, et al. N-Myc gene amp lification is a major
prognostic factor in localised neuroblastoma: results of the French NBL 90
study. J Clin Oncol. 1997 ;15:1171–82.
55. Kushner BH. Neuroblastoma: a disease requiring a multitude of imaging
studies. J Nucl Med.2004;45:1172–88.
56. Hiorns MP, Owens CM. Radiology of neuroblastoma in children. Eur Radiol.
2001;11:2071–81
57. Okazaki T, Kohno S, Mimaya J, et al. Neuroblastoma detected by mass
screening: the Tumor Board's role in its treatment. Pediatr Surg Int.
2004;20:27–32.
58. McHugh K, Pritchard J. Problems in the imaging of three common paediatric
solid tumours. Eur J Radiol. 2001;37:72–8.
59. Hugosson C, Nyman R, Jorulf H, et al. Imaging of abdominal neuroblastoma in
children. Acta Radiol. 1999;40:534–42.
60. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblastoma,
ganglioneuroblastoma, and ganglioneuroma: radio logic -pathologic correlation.
Radiographics. 2002 ;22:911–34.
61. Matthay KK, Villab lanca J, Seeger RC, et al. Treatment of high-risk
neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone
marrow transplantation and 13-c is retino ic acid. N Engl J Med.
1999;341:1165–73.
77 62. Bhansali A, Rajput R, Behra A, et al. Childhood sporadic pheochromocytoma:
clinical profile and outcome in 19 cases. J Pediatr Endocrinol Metab.
2006;19:749–
63. Bonfig W, Bittman I, Bechtold S, et al. Virilis ing adrenocortical tumours in
children. Eur J Pediatr.2003;162:623–8.
64. Dehner L. Pediatric adrenocortical neoplasms: on the road to some clarity. Am
J Surg Pathol.2003;27:1005–7.
65. Michalkiewicz E, Sandrini R, Figueiredo B, et al. Clinical and outcome
characteristics of children with adrenocortical tumours : a report from the
International Pediatric Adrenocortical Tumor Registry.J Clin Oncol.
2004;22:838–45.
66. Stewart JN, Flageole H, Kavan P. A surgical approach to adrenocortical tumors
in children: the mainstay of treatment. J Pediatr Surg. 2004;39(5):759–63.
67. Grundy P, Perlman E, Rosen NS, et al. Current issues in Wilms tumor
management. Curr Probl Cancer. 2005 ;29:221–60.
68. Vujanic GM, Kelsey A, Mitchell C, et al. The role of biopsy in the d iagnosis of
renal tumors of childhood: results of the UKCCSG Wilms Tumor Study 3. Med
Pediatr Oncol. 2003 ;40:18–22.
69. Estrada CR, Suthar AM, Eaton SH, Cilento Jr BG. Renal cell carcinoma:
Children's Hospital Boston experience. Uro logy. 2005;66:1296–300.
70. Geller JI, Dome JS. Local lymph node involvement does not predict poor
outcome in pediatric renal cell carcinoma. Canc er. 2004 ;101:1575–83.
78
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