educational purpose

1. Pathology of Common Childhood
Abdominal Tumor
Presenter – Dr. Gudeta Z (GSR I)
Moderator – Dr Abraham ( Ass’st professor of Pediatric surgery)
Sept 16, 2022
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2. Outline
• Introduction
• Epidemiology
• Nephroblastoma (Wilm’s tumor)
• Neuroblastoma
• Hepatoblastoma
• Rhabdomyosarcoma
• Summary
• References
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3. Introduction
 Cancer in children is uncommon [2% of all ca].
 Second cause of death after trauma for those above 1year.
 Leukemia is the most common form of cancer in children.
 Greatest incidence during 1st year of life.
 Peak 2-3 year , than decline up to 9 year.
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4. Frequency of cancer in childhood
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5. Dashed line cumulative incidence of all cancer
1st peak in early childhood 2nd peak
adolescence
Embryonal
tumors
<1yr
2-3yrs
.>9 yrs
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6. Nephroblastoma (Wilms’ tumor)
 Referred as nephroblastoma or renal embryonal tumor.
 6% of all pediatric tumors.
 2nd common abdominal tumor in childhood.
 Most children presenting between 12-48 months of age.
 Mean age of diagnosis is 36 months.
 Rare at < 6 months of age and after 10 year.
 Bilateral in 4-13 % of children .
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7.  Risk of developing WT in the general population is 1:10,000.
 91% of all renal tumors in childhood.
 Nearly 97% of Wilms’ tumors are sporadic.
10% of children associated with congenital syndrome.
1. WAGR syndrome[ 30%]
2. Beck with-Wiede Mann syndrome [ 43% ]
3. Denys- Drash syndrome (DDS) [ 95%]
4. Hemi hypertrophy
5. Perlman syndrome .
 More common in black race [1:10,000 ].
Epidemiology
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8. Congenital syndromes associated with Wilms’
tumor
Syndromes Characteristics Chromos
om locus
Genetic change Incidence
of WT
WAGR Aniridia, GU malformation ,
Mental retardation , WT
11p13 aniridia gene
(PAX 6) and
(WT1).
>45 %-
50%
Denys-drash Intersexual disorders,
nephropathy, WT
11p13 WT1 point
mutation
>90 %
Beckwith-
wiedemann
Macroglossia,
organomegally,
hemihypertophy, neonatal
hypoglycemia, embryonal
tumor,omphalocele
11p15.5 Dysregulation of
imprinted genes
at chromosome
11p15(Duplicati
on of paternal
allele)
<5 %
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9. Etiology
Genetics and Molecular Biology
 Wilms tumor arise from ;
-Somatic mutations restricted to tumor tissue .
-Germline mutations.
Best characterized gene is WT1, located at 11p13 --sporadic
WT2 is a localized to imprinted genes at 11p15.
Harbor genes for BWS . Leads to abnormal proliferation of
metanephric blastemal cell .
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10. Pathogenesis
• Wilms’ Tumor caused by abnormal renal development ,
• proliferation of metanephric blastema without normal tubular
& glomerular differentiation.
• Nephrogenic rests ; persistent metanephric tissue in the kidney
after the 36th week of gestation
• Genetically WT has been associated with loss of function
mutation of a number of tumor suppressor genes .
WT1 FWT1 & FWT2
P53,PAX6 11p15.5 locus
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11. Pathology
Morphology Grossly :
 Large ,solitary, well
circumscribed mass, and
 Encapsulated (pseduocapsule)
 10 % are either bilateral or
multicentric at the time of
presentation
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12. Cont’d
 On cut section ,the tumor is soft ,homogeneous & tan to gray , with
occasional foci of hemorrhage , cystic degeneration & necrosis
 In many cases there is a lobulated appearance
Microscopically:
The classic WT is triphasic (favorable histology)
Blastemal cells: undifferentiated cells sheets of small blue cells
with few distinctive features.
 Stromal cells: usually fibrocytic or mixoid in nature
 Epithelial cells: abortive tubules or glomeruli
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13. Cont’d
Anaplasia ( unfavorable histology)
• Approximately 5 % of tumors contain foci of anaplasia
• Cells with large, hyperchromatic, pleomorphic nuclei &
abnormal mitoses.
• Anaplasia is the most important predictor of poor out come
- diffuse
- focal
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Favorable histology -packed blue cells consistent with the blastemal
component and interspersed primitive tubules, representing the epithelial
component.
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Anaplasia – Unfavorable Histology cells with hyperchromatic,
pleomorphic nuclei and abnormal mitoses.
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16. Clinical presentation
• Asymptomatic abdominal swelling 60%
• Malaise
• Pain
• Hematuria 15% (gross or microscopic)
• Hypertension 25%
• Anemia
• Metastatic to lungs, liver, regional nodes
 P/E; Firm, non-tender, smooth mass which rarely crosses midline
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17. Differential Diagnosis
 Neuroblastoma can cross midline commonly
 Polycystic kidneys
 Splenomegally
 Obstructive uropathy
 Renal carbuncles
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18. Staging
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19. Neuroblastoma
• Spectrum of tumors that arise from primitive sympathetic
ganglion cells and adrenal medulla
including: - neuroblastoma
- ganglioneuroblastoma
- ganglioneuroma
• Neural crest cells > Neuroblasts > Sympathetic ganglion neuroblastoma.
• 97 % are heterogeneous, varying in terms of location,
histopathologic appearance & biologic characteristics.
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21. Cont’d
• Neuroblastic tumors has broad spectrum clinical behavior,
which can range from
 spontaneous regression,
 maturation to a benign ganglioneuroma, or
 aggressive disease with metastatic dissemination leading
to death.
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22. Epidemiology
• Almost exclusively a disease of children
• 3rd most common child hood cancer.
• Commonest solid extra cranial malignant tumor in the first two
years of life.
• Greater than 525 cases diagnosed each year in US
• Accounts for approximately 6-10% of childhood cancers
• 15 % of all pediatric cancer fatality
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23. Cont’d
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• 1 per 100,000 population
• Median age at diagnosis is 17 month.
• 40% diagnosed before 1 year old.
• Incidence is more in whites than blacks
• Slightly more common among boys.
• 35% during infancy & 5% above 10 years.
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24. Cont’d
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25. Cont’d
 Around 2/3 of primary neuroblastomas arise in the abdomen.
 40% of neuroblastoma arise in the adrenal medulla.
 The reminder occur any where along sympathetic ganglia:
 paravertebral region of abdomen = 25%
 posterior mediastinum = 20%
 other sites (pelvis, neck, brain) =20%
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26. Risk factors
Majority are sporadic
family history in 1-2%
Genetic factors –no
Maternal factors-
• opiate consumption
• folate deficiency
• toxic exposures
• congenital abnormalities
• gestational DM
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27. Pathogenesis
• Adrenal NB are thought to develop from residual microscopic
neuroblastic nodules
• Subsequent malignant transformation result from a failure to
respond to the normal signals that stimulate morphologic
differentiation.
• The origin of extra adrenal nbs is unknown , but presumably
reflects persistent rests of primitive ganglion cells in other
locations as well.
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28. Pathology
Classified according to the balance between neural type
cells & Schwann type cells
- neuroblastomas
- ganglioneuroblastoma
- ganglioneuroma
Neuroblastomas are the most undifferentiated appearing &
aggressive tumors.
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29. Cont’d
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Macroscopically
 Range from minute nodules to large masses weighing 1kg
 Sharply demarcated with a fibrous pseudo capsule,
 Others are more infiltrative & invade surrounding structures (kidney,
renal vein, vena cava & aorta)
 On section - composed of soft, gray-tan, brain like tissue.
 Larger tumors have areas of necrosis , cystic softening & hemorrhage
 Occasionally ,foci of punctuate intra-tumoral calcification can be
palpable.

30. Histology
• Classic Neuroblastomas are composed of small primitive
appearing cells with dark nuclei, scant cytoplasm & poorly
defined cell borders growing in solid sheets.
• Mitotic activity ,nuclear break down, & pleomorphism present.
• Typically, rosettes (homer-Wright pseudo rosette) can be found
in which tumor cells are concentrically arranged.
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31. - Small cells embedded in a finely fibrillar matrix (neuropil).
- Homer-wright pseudorosette(tumor cells arranged concentrically around a central
core of neuropil
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32. Ganglioneuromas
characterized by
• clusters of large cells with
vesicular nuclei
• abundant eosinophilic
cytoplasm, representing
neoplastic ganglion cells
 Spindle shaped Schwann
cells are present in the back
ground stroma
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33. Clinical presentation
 Abdominal tumors
 Abdominal pain or fullness,
 Anorexia
 Weight loss
 Abdominal mass or rarely intestinal obstruction
 Symptoms of compression of venous or lymphatic drainage.
 Mass is typically, but not always, non tender, fixed & firm.
 Pelvic tumors-symptoms of bladder/bowel dysfunction.
 Medstinal tumors- cough, dyspnea, dysphagia, horner syndrome,
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34. Cont’d
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 Cervical tumors - neck mass, stridor, dysphagia.
 Bone - pain/tenderness, swelling, difficulty in walking.
 Paraspinal tumors - abrnormal gait, bladder/bowel.dysfunction
 Skin involvement - bullish subcutaneos nodule.
 Orbital proptosis and periorbital ecchymoses.
 Metastases (lung <3% & intracranial sites- rarely)

35. Staging
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36. Hepatoblastoma
• Occurs predominantly in children <3 yr of age
• The etiology is unknown associated with familial adenomatous
polyposis.
• Incidence is 1 to 2 in 1million births
• Unifocal( completely rescteble)
• Associated with mutations in the β-catenin gene(fap), &
beckwith-wiedemann syndrome.
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37. Pathology
• Grossly the tumor is usually singular, large, brown, & with areas
of hemorrhage & necrosis
• Microscopically: classified as
 Epithelial tumor :- have both fetal & embryonal cells
 Messenchymal tumor:-have fetal, embryonal &
messenchymal tissue
 Small cell or anaplastic HB:- is characterized by small blue
cells with little cytoplasm & hyperchromatic nuclear
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38. Histology
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39. Clinical manifestation
 Weight loss,
 anorexia,
 vomiting &
 abdominal pain
 P/E - Large, abdominal mass ,usually unifocal.
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40. Classification and staging
The children's oncology group (COG) uses the intergroup staging
system for the staging of HB.
Stage I:- the tumor is confined to the liver & totally resected.
Stage II:- the primary liver tumor is resected but there is evidence of
microscopic residual disease in the remaining liver or out side liver.
Stage III:- have either gross tumor left behind positive nodes or tumor
spill at operation.
Stage IV:- have metastatic disease.
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41. Rhabdomyosarcoma
 The most common soft tissue tumor of childhood.
 Approximately one-half of all soft tissue sarcomas.
Epidemiology
 Accounts 3 to 4 percent of pediatric cancers overall.
 350 new cases are diagnosed in the US each year.
 The annual incidence under the age of 20 is 4.3 cases per one
million population
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42. Cont’d
 Any body part can be affected by RMS.
 Rhabdomyosarcomas may occur at any anatomic site but
usually found in
 Head and neck (25%)
 Genitourinary tract (22%)
 Extremities (18%)
 Retroperitoneal
 Other sites account for the remainder of primary sites.
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43. Risk factors
 The etiology and specific risk factors for RMS are not known:
 In-utero radiation
 Low socioeconomic status
 Antibiotics use immediately after birth
 Most are sporadic but the disease has been associated with
familial syndromes such as
 Neurofibromatosis
 Li-fraumeni
 Beckwith-wiedemann
 Costello syndromes
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44. Histology
• Embryonal RMS = 60%
with an intermediate
prognosis
• Composed of typical
rhabdomyoblasts arranged in
sheets and large nests, with
infrequent intermixed
fusiform cells.
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45. Cont’d
Botryoid variant
 “ grape-like” gross appearance
of the tumor
 the polypoid mass grows
beneath an epithelial surface,
and subepithelial dense
aggregates of rhabdomyoblast
 typically arises within the wall
of the bladder or vagina and is
seen almost exclusively in
infants.
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46. Cont’d
Alveolar RMS
• fibrovascular septae that are lined
with densely packed ovoid to
round tumor cells, and
• separated by pseudo-alveolar
spaces, which vaguely resemble
pulmonary alveoli.
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47. Anaplastic RMS
 presence of large
hyperchromatic nuclei, with
atypical bizarre mitotic figures
 nuclear size is threefold larger
than that of adjacent "typical"
tumor cells.
Undifferentiated sarcoma
 lack any defining cytologic or
architectural features,
 typically large nests of tumor
cells that have vesicular nuclei
and large nucleoli
 lack the eosinophilic
cytoplasm characteristic of
myogenic differentiation
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48. Clinical Presentation
• The presenting signs and symptoms of RMS are variable, and
are influenced by the
 site of origin, the
 age of the patient, and the
 presence or absence of distant metastases.
• In general, the primary lesion has the appearance of a non
tender mass, occasionally with overlying skin erythema.
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49. Summary
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50. References
 Coran pediatric surgery, 7th edition
 Ashcraft pediatric surgery,6th edition
 Uptodate 21.6.
 Robins pathology, 10th Edition
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