Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st Year, 2nd Year, 3rd Year and Final year Pediatric Surgery 6 Common Paediatric Solid Tumours PPT-Powerpoint Presentations and lecture notes
Common paediatric
solid tumours
The malignant solid tumors of children
are histological y very diverse and a
substantial proportion consists of
characteristic entities that are rarely
seen in adults.
Introduction
They have been classified and
categorized
by
International
Classification of Childhood Cancers, (3rd
ed.) into 12 groups which are further
divided into subgroups and divisions.
1. Leukemias, myeloproliferative diseases, and myelodysplastic diseases
2. Lymphomas and reticuloendothelial neoplasms
3. CNS and miscel aneous intracranial and intraspinal neoplasms
4. Neuroblastoma and other peripheral nervous cel tumors
5. Retinoblastoma
6. Renal tumors
7. Hepatic tumors
8. Malignant bone tumors
9. Soft tissue and other extraosseous sarcomas
10. Germ cel tumors, trophoblastic tumors, and neoplasms of gonads
11. Other malignant epithelial neoplasms and malignant melanomas
12. Other and unspecified malignant neoplasms
Neuroblastoma
? One of the most common solid tumours of the infancy and childhood.
? Neoplasm of the neural crest origin.
? Clinical course variable-highly malignant tumour demonstrates
unusual behaviour:
? Spontaneous regression
? Tumour maturation from a malignant to a benign histologic
? Progressive disease
? Clinical incidence 1 in 7500-10000 children.
? 10% of all childhood tumours and 15% of all cancer deaths.
? Approx. 40% cases are diagnosed by 1year of age, 75% by 7 years and
98% by 10years.
? Slightly more common in boys than girls.(1.2:1).
? Most common intra-abdominal malignancy in newborns.
? Most frequently diagnosed malignancy in children less than 1 year of
age.
? Embryonal nature of neuroblastoma- invade the placenta during the
antenatal period.
? Mothers of infants with congenital neuroblastoma occasionally experience
flushing and hypertension
? release of catecholamines from the fetal tumour in utero.
? Familial neuroblastoma: hereditary factors present:
? Described in twins and family members
? Median age for the occurrence of familial neuroblastoma is 9 months, in
contrast to 18 months in the general population.
? 20% of patients with familial neuroblastoma have bilateral or multifocal
tumors.
? Locus on chromosome 16p12-13
OTHER ASSOCIATED SYNDROMES
? Beckwith Weidmann syndrome
? Neurofibromatosis (von Recklinghausen disease)
? Hirschsprung's disease
? Central hypoventilation syndrome (ondine's curse)
? Fetal alcohol syndrome
? Offsprings of mothers taking phenytoin for seizure disorder (fetal
hydantoin syndrome)
SITES
? Neuroblastoma may occur at any site where neural crest tissue is found in
the embryo.
? Tumours may arise in the neck, posterior mediastinum, retroperitoneal
(paraspinal) ganglia, adrenal medulla, and pelvic organ of Zuckerkandl.
? In 75% of cases, the tumour is located in the retroperitoneum
? the adrenal medul a (50%)
? the paraspinal ganglia(25%).
? In 20% of cases, the primary tumour is in the posterior mediastinum.
? Less than 5% of tumours occur in the neck or pelvis.
? Primary intracranial cerebral neuroblastoma also occurs.
CLINICAL PRESENTATION
? Neuroblastoma is a tumour with multiple clinical manifestations
related to:
? site of the primary tumour
? Presence of metastases
? production of certain metabolic tumour by-products.
SITE OF THE PRIMARY TUMOR: ABDOMEN
? Abdominal mass(50-70%)-hard, nodular, fixed and painful on palpation.
? Occasional y, large tumours can result in compression of venous and
lymphatic drainage from the lower extremities, leading to scrotal and
lower extremity oedema.
? Rarely, patients wil experience renin-mediated hypertension because of
compromise of renal vasculature.
? Hemoperitoneum caused by sudden spontaneous rupture of the neoplasm.
? Paraspinal tumours
? may manifest with paraplegia related to tumour extension through an
intervertebral foramen, resulting in a dumbbell- or hourglass-shaped lesion
that may cause extradural compression of the spinal cord.
? Pelvic- may be palpable on rectal examination.
? Cauda equina syndrome.
? Severe back ache
? Saddle anaesthesia-including the perineum, external genitalia and anus with numbness
or "pins-and-needles" sensations of the groin and inner thighs which would contact a
saddle when riding a horse.
? Bladder and bowel dysfunction
? Weakness of the muscles of the lower legs (often paraplegia)
? Gait disturbance
UPPER MEDIASTINUM OR NECK
? Neoplasms arising in the upper mediastinum or neck may involve the
stellate ganglion and cause Horner syndrome, which is characterized
by ?Ptosis
? Miosis
? Enophthalmos
? Anhydrosis
? heterochromia of the iris on the affected side.
MEDIASTINAL TUMOURS
? Respiratory distress because of the tumour's interference with lung
expansion and dysphagia caused by extrinsic pressure on the
oesophagus.
? May manifest with paraplegia.
METASTASIS
? Neuroblastoma may spread by direct extension into surrounding
structures, lymphatic infiltration, or hematogenous metastases.
? Regional and distant lymph nodes, liver, bone marrow, and bone cortex are
frequently involved.
? Patients with bone cortex metastases- ominous prognosis. Bone
metastases occur in sites containing red marrow and involve the
metaphyseal areas of long bones in addition to the skull, vertebral column,
pelvis, ribs, and sternum.
? Bone lesions may cause extreme pain and may be first identified when a child
refuses to walk because of leg pain.
? Haematogenous metastases-brain, spinal cord, and heart.
? Brain metastases usually manifest in older children with headaches
and seizures.
? Lung metastasis-result of direct extension to the lung from
mediastinal lymph nodes or diffuse haematogenous spread,
presenting with a radiographic pattern that may be confused with
pulmonary oedema or interstitial pneumonia.
? Metastases to the bony orbit may produce proptosis or bilateral
orbital ecchymosis--often referred to as "panda eyes" or "raccoon
eyes".
? Anemia is often related to bone marrow invasion by the tumor.
? Bleeding diathesis related to thrombocytopenia from extensive
involvement of bone marrow and interference with hepatic
production of clotting factors by liver metastases.
? Massive involvement of the liver with metastatic disease is
particularly frequent in infants with stage 4S and may result in
respiratory compromise (Pepper Syndrome).
? Multiple subcutaneous skin nodules- stage 4S
? non-tender, bluish and mobile- called the "blueberry muffin sign"
PRODUCTION OF CERTAIN METABOLIC
TUMOR BYPRODUCTS
? Excessive catecholamine production by the tumour may result in
flushing, sweating, and irritability.
? Hypertension(25% of cases)
? Acute cerebellar ataxia, characterized by opsomyoclonus and
nystagmus ("dancing eye syndrome"):
? seen more frequently (>60%) in patients with primary mediastinal tumours, in
patients with stage I or II disease, and in infants younger than 1 year of age.
? autoimmune phenomenon related to an antigen?antibody complex involving
antibodies that cross-react with Purkinje cells in the cerebellum.
? Poor school performance and learning deficits may occur as sequelae.
? The survival rate for patients is 90%.
? Persists even when the tumour is removed.
? Intractable diarrhea characterized by watery, explosive stools and
hypokalemia. The diarrhea is related to the production of vasoactive
intestinal polypeptide (VIP) by the tumour.
? Often have somatostatin receptors and are differentiated, low-risk tumours.
? Serum VIP levels can serve as a tumour marker
? Tumour often does not secrete catecholamines.
? somatostatin receptor expression is a favourable prognostic factor.
DIAGNOSIS: LABORATORY FINDINGS:
? Lactate Dehydrogenase:
? High serum levels of LDH- high proliferative activity or large tumour burden.
? LDH level higher than 1500 IU/L-poor prognosis
? Ferritin:
? High levels of serum ferritin (>150 ng/mL)-reflect a large tumour burden or
rapid tumour progression.
? Elevated serum ferritin is often seen in advanced-stage neuroblastomas and
indicates a poor prognosis.
? Neuron-Specific Enolase:
? Another useful prognostic marker of advanced-stage neuroblastoma-
correlate with tumour burden.
? The incidence of elevated NSE levels increases with stage.
? A serum level of NSE >100 ng/mL - poor outcome.
? Catecholamine or their Metabolites:
? Neuroblastoma-secretion of catecholamine products, the metabolites of
which can be detected in the urine of more than 90% of patients.
? Urine specimen is of clinical value in diagnosing neuroblastoma and
determining the response to therapy.
? Urinary levels of vanillylmandelic acid (VMA) and homovanillic acid (HVA) can
also be used as markers of tumour progression or relapse, and serve as a
surrogate prognostic indicator.
? 24-hour urine estimations for younger children.
Diagnostic Imaging
? Standard Radiographs:
? Chest radiography- presence of a posterior mediastinal mass.
? Abdominal radiography is less often the modality by which a neuroblastoma
is discovered- as a mass with fine calcification(50%).
? Paraspinal widening is commonly found with celiac axis tumors.
? Ultrasonography:
? Most often used during the initial assessment of a suspected abdominal mass.
? Sensitivity and accuracy are less than that of CT or MRI for diagnosing
neuoblastoma.
? Computed Tomography :
? CT can demonstrate calcification in almost 85% of neuroblastomas
? Intraspinal extension of the tumor can be determined on contrast-enhanced
CT.
? Overall, contrast-enhanced CT has been reported to be 82% accurate in
defining neuroblastoma extent, with the accuracy increasing to nearly 97%
when performed with a bone scan.
? Magnetic Resonance Imaging:
? MRI is the most useful and most sensitive imaging modality for the diagnosis
and staging of neuroblastoma.
? More accurate than CT for detection of stage 4 disease.
? Sensitivity of MRI is 83%, and that of CT is 43%
? Specificity of MRI is 97%, and that of CT is 88%.
? Metastases to the bone and bone marrow, in particular, are better detected
by MRI, as is intraspinal tumor extension.
? When considering skeletal metastases alone, MRI and bone scan have been
shown to be equivalent.
? Encasement of major vessels can be better defined by MRI than CT, especially
with the use of MR angiography.
Metaiodobenzylguanidine Imaging
? Metaiodobenzylguanidine (MIBG) is transported to and stored in the
chromaffin cells in the same way as norepinephrine.
? Preferred imaging study for evaluating the bone and bone marrow
involvement by neuroblastoma.
? Primary tumors and lymph node metastases are also detectable.
? Technetium-99m methylene diphosphonate(99mTc-MDP) bone scans
is a second choice if MIBG imaging is not available or does not
visualize known disease.
? Bone Marrow Examination:
? Marrow biopsy is a routine method for detecting bone marrow involvement.
? Both aspiration and trephine biopsy should be performed, although the latter
has better diagnostic value.
STAGING
? In 1988, an international staging system was devised.
? This system takes into account:
? tumor size and location relative to the midline
? presence and degree of metastatic disease.
? extent of surgical resection of the primary tumor in patients with
nonmetastatic disease.
Pathology
? On histological examination, the immature neuroblasts appear as
sheets of dark-blue nuclei with scanty cytoplasm set in a delicate
vascular stroma.
? More differentiated areas show the presence of ganglion cells with a
more abundant stroma.
? Rosette formation may be observed and is considered a sign of early
tumor differentiation. The center of each rosette is formed by a
tangle of fine nerve fibers.
MOLECULAR BIOLOGY
? DNA Content:
? The majority (55%) of primary neuroblastomas are triploid or `near-
triploid/hyperdiploid'
? Remainder (45%) are either `near-diploid' or `near-tetraploid'.
? Neuroblastomas that are near-diploid or near-tetraploid usual y have
frequently chromosome 1p deletion and MYCN amplification.
? Patients with near-triploid tumors typical y have favourable clinical and
biologic prognostic factors and excel ent survival rates.
? Amplification of MYCN
? MYCN encodes a 64 kDa nuclear phosphoprotein that is located at
chromosome 2p24).
? Approx. 25% of primary neuroblastomas in children have MYCN
amplification
? MYCN amplification being present in 40% with advanced disease
but only 5?10% with low-stage disease.
? Amplification of MYCN is associated with advanced stages of
disease, rapid tumour progression, and poor outcome.
? Chromosomal Changes:
? 1p deletions.
? Deletion of the long arm of chromosome 11 (11q) is also common in
neuroblastoma(40% of cases).
? Unbalanced deletion of 11q is inversely related to MYCN amplification.
? Other Molecular Abnormalities:
? Trk A appears to mediate differentiation of developing neurons or
neuroblastoma.
? High Trk A expression is associated with favorable tumor.
Treatment
? For stage 1 or 2 disease, surgery alone may be sufficient or associated with
neoadjuvant and adjuvant chemotherapy.
? Initial chemotherapy is mandatory for children with stage 3 or 4 disease.
Immediate surgery for those with local y advanced disease is markedly
more difficult and unsatisfactory.
? In some children with stage 4S disease, no treatment is necessary and the
disease resolves spontaneously.
? Treatment is required in the face of relentless hepatomegaly causing respiratory
compromise.
? Combination chemotherapy may include cyclophosphamide,
vincristine, cisplatin, carboplatin, doxorubicin and etoposide, among
others.
? Radiotherapy- Neuroblastoma is a radiosensitive tumour.
? Radiotherapy is usually used in advanced stages or myeloablative therapies.
? Immunotherapy is also being used.
? The goal of resection is a complete dissection of the vasculature and
should include the primary tumour site, in addition to all regional
lymph nodes.
? Neuroblastoma often adheres to or surrounds the great vessels, and
special care should be taken to identify and spare the blood supply to
important visceral structures, such as the branches of the celiac axis
and superior mesenteric artery.
? Because neuroblastoma may have a friable pseudocapsule, careful
handling of the tumour during dissection is important to avoid tumor
spill and haemorrhage.
Wilm's tumour
Wilms' Tumour(Nephroblastoma)
? Max Wilms (1867?1918), Professor of Surgery in Heidelberg, described the
tumour that stil bears his name in 1899.
? Wilms tumour (WT, nephroblastoma) is the most common renal tumour of
childhood and the second most common intra-abdominal malignancy after
neuroblastoma.
? The risk of developing WT in the general population is 1:10,000.
? The incidence is slightly elevated for American and African blacks
compared with whites and is significantly lower in Asians.
? The mean age at diagnosis is 36 months, with most children presenting
between the ages of 12 and 48 months.
? Tumours tend to occur about 6 months later in girls than in boys.
? Tumours can be unilateral or bilateral.
? Bilateral Wilms(4-13%) is common in congenital syndromes.
? WAGR syndrome (WT, aniridia, genitourinary malformation, mental
retardation) is a rare genetic syndrome associated with a chromosomal
defect in 11p13.
? Children with WAGR syndrome are at a 30% higher risk of developing WT than a
normal child.
? Beckwith-Wiedemann syndrome (BWS) is a congenital disorder of growth
regulation, affecting 1 in 14,000 children.
? Children with BWS have visceromegaly, macroglossia, omphalocele, and
hyperinsulinemic hypoglycemia at birth.
? They also have an increased risk of tumor development.
? The most common tumours associated are hepatoblastoma, WT and neuroblastoma.
? Denys-Drash syndrome (DDS) (nephropathy, renal failure, male
pseudohermaphroditism, and WT) is also associated with an
increased risk of WT.
? Some investigators have recommended prophylactic nephrectomy in children
with this syndrome once they develop renal failure
? Other syndromes are:
? Hemihypertrophy
? Pearlman syndrome
Molecular Genetics of Wilms Tumor
? Multiple mutated WT genes have been identified as well as areas of
loss of genetic material and allelic uniqueness (loss of heterozygosity)
that are important to tumor development.
? TP53
? TP53 mutations in WT are almost exclusively found in tumors with anaplastic
histology.
? 75% of anaplastic WT have p53 mutations.
? p53 mutations may be essential for anaplastic progression.
? CTNNB1
? CTNNB1 mutations have been reported to occur in 15% of WT.
? WTX
? The WTX gene (also known as AMER1 for adenomatous polyposis coli (APC)
membrane recruitment 1) was found to be mutated in 29% WT.
? It is the most common known gene mutation in WT.
? It is located on X chromosome.
? WT1
? WT1 gene was the first gene to be linked with WT development.
? It is located at chromosome 11p13.
? WT2
? This second WT gene location was identified by linkage analysis in children
with BWS.
? It is located at 11p15.
? Loss of Heterozygosity
? LOH refers to loss of genetic material and allelic uniqueness.
? Outcomes for patients with LOH at 1p and 16q were at least 10% worse than
those without LOH.
? DNA ploidy
? DNA index greater than 1.5 was strongly associated with anaplastic histology
and predictive of poor outcome.
Clinical Presentation
? Most children with WT present with an asymptomatic abdominal mass, often
discovered incidentally.
? Abdominal pain is second most common presentation.
? Gross hematuria (18.2% of patients) and microscopic hematuria (24.4%).
? 10% of children with WT have coagulopathy.
? 20% to 25% present with hypertension because of activation of the renin-
angiotensin system.
? Fever, anorexia, and weight loss occur in 10%.
? Extension of tumour thrombus into the renal vein can obstruct the spermatic vein
and result in a left varicocele.
? In rare cases, tumour extension into the atrium may produce cardiac malfunction.
? Tumour rupture and haemorrhage are also infrequent events that can present as
an acute abdomen.
Diagnosis
? Ultrasonography (US) is a good screening examination of a mass to
determine its site of origin and to assess for possible intravascular or
ureteral extension.
? About 4% of WT present with inferior vena cava (IVC) or atrial involvement
and 11% with renal vein involvement.
? A computed tomography (CT) scan of the abdomen will confirm the
renal origin of the mass and determine whether there are bilateral
tumors.
? The common sites of metastatic spread are the lungs and the liver.
Therefore, in addition to abdominal imaging, pulmonary imaging
must be performed.
? Trucut needle biopsy under ultrasound guidance is confirmatory.
? Helps to know favourable and unfavourable histology.
? DMSA
? For planning of bilateral tumours.
Pathology
? WT are embryonal tumors containing components seen in normal
developing kidneys.
? The classic WT consists of three elements:
? blastemal, stromal, and epithelial tubules.
? Anaplastic tumours are aggressive and bear unfavourable histology.
Socie?te? Internationale d'Oncologie
Pe?diatrique (SIOP) Staging Systems
Stage Criteria
1
The tumor is limited to the kidney or surrounded with a fibrous pseudocapsule, if outside the normal contours of the
kidney. The renal capsule or pseudocapsule may be infiltrated with the tumor, but it does not reach the outer
surface, and it is completely resected. The tumor may be protruding (bulging) into the pelvic system and dipping into
the ureter, but it is not infiltrating the walls. The vessels of the renal sinus are not involved. Intrarenal vessels may
be involved.
2
The tumor extends beyond the kidney or penetrates through the renal capsule and/or fibrous pseudocapsule into
the perirenal fat, but it is completely resected. The tumor infiltrates the renal sinus and/or invades blood and
lymphatic vessels outside the renal parenchyma, but it is completely resected. The tumor infiltrates adjacent organs
or vena cava, but it is completely resected. The tumor has been surgically biopsied (wedge biopsy) prior to
preoperative chemotherapy or surgery.
3
There is incomplete excision of the tumor, which extends beyond resection margins (gross or microscopic tumor
remains postoperatively). Any positive lymph nodes are involved. Tumor ruptures before or during surgery
(irrespective of other criteria for staging). The tumor has penetrated the peritoneal surface. Tumor implants are
found on the peritoneal surface. The tumor thrombi present at resection, margins of vessels or ureter are transected
or removed piecemeal by surgeon.
4
Hematogenous metastases (lung, liver, bone, brain, etc.) or lymph node metastases are outside the abdominopelvic
region.
5
Bilateral renal tumors present at diagnosis. Each side has to be substaged according to above classifications.
PROGNOSTIC FACTORS
? Histology: Most important prognostic factor.
? Stage: Higher the stage poor is prognosis. Second most important
prognostic factor.
? Rapid response: This is a prognostic category being evaluated in
patients who have stage IV disease that is based on lung metastasis
alone. The goal in these patients is to avoid lung radiation. Response
to therapy is also being assessed in bilateral disease.
? Loss of heterozygosity: LOH at both 1p and 16q are now used as
determinants of therapy.
Chemotherapy
? Actinomycin- D is the major chemotherapeutic agent used.
? Other active chemotherapeutic agents are vincristine, doxorubicin,
and cyclophosphamide.
? For children with favorable-histology stage I and II tumors without
LOH, 18 weeks of vincristine and dactinomycin is recommended.
? For children with FH stage II and IV tumors without LOH, 24 weeks of
vincristine, dactinomycin, and doxorubicin is recommended.
? For those patients who have positive LOH at both loci (1p and 17q),
treatment will be intensified.
Surgery
? Routine preoperative chemotherapy is administered for 4-6 cycles
and nephrectomy being carried out at five to six weeks.
? Immediate surgery is indicated in the following situations:
? ruptured tumour at presentation (emergency)
? largely cystic tumour (not possible to biopsy, relatively insensitive to
chemotherapy)
? doubt in diagnosis, despite needle biopsy
? infants under six months of age (likelihood of mesoblastic nephroma,
increased difficulties in chemotherapy).
? Approach is always through transperitoneal approach via a generous
transverse upper abdominal supraumbilical incision.
? The renal artery should be ligated before the renal vein to avoid
sequestration of blood within the tumour, congestion and rupture.
? Before dividing the renal vein, it should be inspected carefully and
vascular clamps applied so that any tumour extension can be seen
and extracted.
Intracaval extension
? If the extension is infrahepatic, it can be extracted safely by cavotomy
alone.
? If intrahepatic or intra-atrial, the operation should be planned with a
paediatric cardiac surgeon and cardiopulmonary bypass must be
available.
Bilateral Wilms
? Two options:
? Bilateral partial nephrectomy.
? Most involved side total nephrectomy and partial nephrectomy on the other
side.
OUTCOME
? Stage I: 90?95 per cent.
? Stage II: 80?90 per cent.
? Stage II : 80?85 per cent.
? Stage IV: 70?75 per cent.
? Stage V: 80?85 per cent.
Rhabdomyosarcoma
? Rhabdomyosarcoma is a soft tissue malignancy that accounts for
approximately 4% of all pediatric malignancies.
? Derived from embryonic mesenchymal cells that can later
differentiate into skeletal muscle.
? Incidence is 4.3 cases/million children, with approximately 350 new
cases diagnosed annually.
? Bimodal peak incidence
? Ages of 2 and 5 years and again from 15 to 19 years of age.
? Almost 50% are diagnosed before the age of 5 years.
? Most cases occur sporadically, with no recognizable risk factors.
? Occurs with increased frequency in patients with
? neurofibromatosis type I
? Li-Fraumeni syndrome
? Beckwith-Wiedemann syndrome
Sites of Involvement
? Rhabdomyosarcoma can appear at any site in the body, including those
that do not typical y contain skeletal muscle.
? Most common sites in children are:
? head and neck (35%)
? Genitourinary tract (25%)
? extremities (20%).
? Less common primary sites include the trunk, GI tract, intrathoracic, and
perineal regions.
? Head and neck lesions tend to occur in the parameningeal region, orbits,
and pharynx.
? Other specific sites include the bladder, prostate, vagina, uterus, liver,
biliary tract, paraspinal region, and chest wal .
Pathology
? Pathological y classified into three types:
? Embryonal
? Alveolar
? pleomorphic.
? Embryonal rhabdomyosarcoma is the most common type(2/3rd). Two
subtypes of embryonal rhabdomyosarcoma--botryoides and spindle cel --
appear to be associated with a better prognosis than others of similar
histology.
? On examination of a sample, characteristic rhabdomyoblasts may be
present.
? Immunohistochemical staining for muscle-specific proteins, such as myosin
and actin, desmin, and myoglobin, can bolster the diagnosis.
Clinical Presentation
? Manifestations of rhabdomyosarcoma depend on its size, location,
age of the patient, and presence of metastatic disease.
? The mass is typically asymptomatic, although most symptoms are
related to compressive effects and can result in pain.
? Orbital tumors can produce proptosis, decreased visual acuity, and
ophthalmoplegia.
? Those arising from parameningeal sites frequently produce
headaches and nasal or sinus obstruction that can be accompanied by
a mucopurulent or bloody discharge. Moreover, these tumors can
invade intracranially to produce cranial nerve palsies.
? For genitourinary rhabdomyosarcoma, paratesticular tumors may
present as painless swelling in the scrotum, which may be confused
with a hernia, hydrocele, or varicocele.
? Bladder tumors, commonly located at the base and trigone, result in
hematuria and urinary obstruction.
? Prostate tumors can cause polyuria and constipation caused by
compression of the bladder or bowel.
? Vaginal tumors in girls present with a protruding mass or vaginal
bleeding and discharge.
? In the case of extremity rhabdomyosarcoma, distal involvement is
more common than proximal, and the lower extremities are more
commonly involved than the upper extremities.
? These tumors present as a painless mass, and some children may develop a
limp or disuse of the affected limb.
? At the time of diagnosis, almost 50% of patients have regional lymph node
metastasis.
? Retroperitoneal tumors can grow large, making them difficult to
resect. Symptoms arise secondary to invasion of adjacent structures
and the associated pain and distention are typical late features of
disease.
? Biliary tract tumors comprise 0.8% of all rhabdomyosarcomas and,
like other signs of biliary obstruction, patients present with jaundice,
abdominal swelling, fever, and loss of appetite.
Diagnosis and Staging
? The patient should be thoroughly examined and diagnostic imaging and basic laboratory
studies performed.
? With concern for parameningeal involvement, cerebrospinal fluid should also be
evaluated.
? There are no specific serum tumor markers for diagnosis.
? Depending on tumor location, MRI or CT should be used to characterize the mass better
and evaluate for adjacent structural invasion, vessel encasement, metastasis, and
adenopathy.
? One of the most critical aspects of the diagnostic process is obtaining tissue for histologic
confirmation, which is usual y accomplished by an incisional or core needle biopsy.
? On confirmation, surgical resection can be completed, although it may necessitate
preoperative chemotherapy for tumor shrinkage.
? It should also be noted that during preoperative planning, the biopsy site should also be
excised because there can be local recurrence.
? Based on histologic variances, rhabdomyosarcoma subtypes are
associated with prognosis.
? Botryoid (cluster of grapes) and spindle cell sarcomas are noted to
have a favorable prognosis
? Embryonal and pleomorphic histologies have an intermediate
prognosis
? Alveolar and undifferentiated histologies exhibit a poor prognosis.
? Pretreatment staging serves to stratify patients, determine the most
appropriate treatment regimen, and compare outcomes.
? Because it relies on preoperative imaging, this is technically clinical
staging, although it is still based on TNM criteria
? It should be stressed that intraoperative or pathologic results from
resected samples should have no bearing on patient stage. This is
reserved for what is known as clinical grouping, which consists of
selection into a group depending on operative findings, pathology,
margins, and node status.
? Taken together, clinical grouping and pretreatment staging have been
shown to correlate with outcomes.
Staging for Rhabdomyosarcoma
? Group I: Localized disease that is completely resected, with no regional
node involvement
? Group I
? A: Localized, grossly resected tumor with microscopic residual disease but no
regional nodal involvement
? B: Locoregional disease with tumor-involved lymph nodes with complete resection
and no residual disease
? C: Locoregional disease with involved nodes, grossly resected, but with evidence of
microscopic residual tumor at the primary site and/or histologic involvement of the
most distal regional node (from the primary site)
? Group I I: Localized, gross residual disease including incomplete resection,
or biopsy only of the primary site
? Group IV: Distant metastatic disease present at time of diagnosis
? Low-risk patients have an estimated 3-year failure-free survival rate
of 88%.
? Intermediate-risk patients have an estimated 3-year failure-free
survival rate of 55% to 76%.
? High-risk patients have a 3-year failure-free survival rate less than
30%.
Treatment
? The main goal of therapy is to achieve cure or, if that is not feasible,
at least to obtain local control.
? Multimodality approach, with a combination of surgery,
chemotherapy, and radiation therapy. Equally important is the need
to minimize the short- and long-term effects of therapy.
? Currently, all patients with rhabdomyosarcoma receive some
combination chemotherapy because it improves progression-free and
overall survival.
? The recommended regimen depends on the risk stratification,
? low-risk patients subgroup A- vincristine and dactinomycin
? low-risk subgroup B and higher, cyclophosphamide is added to above therapy.
? Radiation therapy has been found to be effective for the local control
of rhabdomyosarcoma, especially in patients who have microscopic
disease after resection.
? It has also been successfully used in patients in whom surgery could
result in significant disfigurement, such as with head and neck lesions.
? As is the case with most surgical approaches, a complete resection
with negative margins and nodal sampling is the mainstay of
treatment.
? The specific operative guidelines depend on the location of the tumor.
? For head and neck tumors that are superficial and nonorbital, wide
excision of the primary tumor with sampling of ipsilateral cervical
lymph nodes is acceptable.
? Parameningeal lesions are particularly difficult to resect completely,
given their degree of extension into critical structures. In these
patients, and in patients with tumors that are considered
unresectable, chemotherapy and radiation therapy are first-line
treatment.
? For extremity lesions, it is important to achieve complete resection
through wide local excision. Amputation is rarely necessary, except
for distal tumors in the hand or foot that involve neurovascular
structures.
? Given that trunk and extremity lesions have a high incidence of lymph
node metastasis, sentinel lymph node mapping is being increasingly
recommended.
? Reexcision may also be considered with evidence of minimal residual
disease after initial resection.
? Patients with extremity tumors receive combination chemotherapy
but, because of the high incidence of the alveolar histology,
radiotherapy is also often used.
? The approach for patients with genitourinary tumors depends on which organ is
affected.
? Preservation of bladder function is the key in resection of tumors involving the bladder or
prostate.
? If this goal cannot be met, preoperative chemoradiation is usually recommended.
? If residual disease remains despite this, more aggressive measures can be considered,
including a partial cystectomy, prostatectomy, or anterior (rectum-sparing) exenteration.
? Patients with paratesticular rhabdomyosarcoma should undergo a radical
inguinal orchiectomy with a retroperitoneal lymph node dissection in boys
younger than 10 years because of the frequent prevalence of metastasis.
? When the tumor is clearly fixed to scrotal skin, resection is required.
? Chemotherapy is standard, whereas radiation therapy is indicated only with positive nodes.
? For patients with vaginal or vulvar rhabdomyosarcoma, vaginectomy and wide
local excision, respectively, and multiagent chemotherapy are recommended.
Outcomes
? Approximately 15% of children present with metastatic disease and their
prognosis remains poor.
? Approximately 30% of patients with rhabdomyosarcoma wil relapse, and
50% to 95% of them wil die as the disease progresses.
? Median survival from the first recurrence is 0.8 years, with an estimated 5-
year survival rate of only 17%.
? Rhabdomyosarcoma is a curable disease in most children, with more than
60% surviving 5 years after diagnosis.
? Survival for children with this malignancy has improved secondary to a
number of factors, including better imaging and pathologic classification,
use of multiagent chemotherapy, and appropriate use of radiotherapy.
This post was last modified on 08 April 2022