The document discusses several pediatric neoplasms that appear as small round blue cell tumors due to their primitive histological features. These include neuroblastoma, Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, medulloblastoma, retinoblastoma, and lymphoma. For each tumor, the document outlines characteristics such as common age of diagnosis, clinical features, histopathological appearance under the microscope, immunohistochemistry profiles, genetics where relevant, and important prognostic factors. Differential diagnosis of these small round blue cell tumors in children is provided for accurate diagnosis and treatment.

1. Moderator:-Dr. Poonam Nanwani
Speaker:- Dr. Narmada Prasad Tiwari

2. Histologically, many of the pediatric neoplasms have
more primitive origin characterized by sheets of
cells ,with small , round nuclei.
Because of their primitive histologic appearance
many childhood tumor have been collectively referred
to as small round blue cell tumor.

3. The differential diagnosis of such tumors are:-
Neuroblastoma
Wilms tumour(Nephroblastoma)
Rhabdomyosarcoma
Ewing’s sarcoma/PNET
Medulloblastoma
Retinoblastoma
Lymphoma

4. NEUROBLASTOMA
 most common extracranial solid tumor of
childhood
most frequently diagnosed tumor of infancy.
Median age at diagnosis is 21 months.
Most occur sporadically.
1 to 2% occur familial- Germ line mutation in the
anaplastic lymphoma kinase (ALK) gene

5. Clinical course-
In childhood 40% of neuroblastoma arise in
adrenal medulla.
Other sites-along sympathetic chain
post. Mediastinum
neck, brain.
• under 2 year - large abdominal mass, fever
,weight loss.
About 90% of neuroblastoma regardless of
location produce catecholamines.
Neuroblastoma – size- minute nodules to large
masses

6. Gross-

7. Neuorblastoma Morphology
Small round blue cell tumor
neuorpil formation (fibers, i.e., axons dendrites, mostly
unmyelinated)
rosette formation
immunochemistry – neuron specific enolase
EM – secretory granules (catecholamine)
Usual features of anaplasia
high mitotic rate is unfavorable
evidence of Schwann cell or ganglion differentiation
favorable

8. Histologically

9. Undifferentiated type

10. Differentiating type
Poorly differentiated type

11. Neuroblastoma may metastasize widely through the
hematogenous & lymphatic system, particularly to
liver, CNS, bone, lymph nodes and bone marrow.

12. Prognostic factors in neuroblastoma
Variable Favourable Unfavourable
(1) Stage 1, 2A,2B,4S 3,4
(2) Age <18 month > 18 month
(3)Histology:-
(a)Evidence of schwannnian stroma
& gangliocytic differentiation.
(b) Mitosis-karyorrhexis index
Present
< 200/5000 cells
Absent
>200/5000 cells
(4) DNA ploidy Hyperdiploidy or
near triploidy
Near diploid
(5) N-Myc Not amplified Amplified
(6) Chromosome 17q gain Absent Present
(7) Chromosome 1 p loss Absent Present
(8) Chromosome 11q loss Absent Present
(9) Trk A expression Present Absent
(10)TrkB expression Absent Present
(11) Telomerase expression Low or Absent Highly
expressed.

13. WILMS’ TUMOR(NEPHROBLASTOMA)
Age:- 3 -6 years
Sex:- No sex predeliction
Clinical features-Large abdominal mass
Hematuria
Pain in abdomen
Hypertension

14. Molecular Genetic
Genetic loci predisposing to wilms’ tumor are
WT1 ( located on chromosome 11p 13 )
WT2 ( located on chromosome 11p 15.5 )
- Mutations of B catenin gene-14-20%
- Conditions associated with wilms’ tumor are:-
WAGR syndrome:-
Wilms’ tumor
Aniridia
Genital anomalies
Retardation

15. Beckwith wiedemann Syndrome:-
Omphalocele
Macroglossia
Hemihypertrophy of organs
Denys Drash Syndrome:-
Gonadal dysgenesis( male psuedohermaphroditism)
Early onset nephropathy

16. Gross:- solid, well circumscribed.
On cut-:-solid & pale gray & often exhibit areas of
cystic changes, necrosis & hemorrhage.

18. Microscopically :- Three major component are
identified.
I- Undifferentiated blastema
II – Mesenchymal ( stromal) tissue
III – Epithelial tissue
Blastematous - small round to oval cells,
scanty cytoplasm
The mesenchymal element- spindle cell
fibroblast like configuration.
Epithelial component- embryonic glomerular
and tubular structures.

21. Additional morphological features-
Ciliated,mucinous, squamous or transitional
epithelium, neuroepithelium,mature adipose
tissue,Cartilage & bone

22. Anaplastic wilms tumour

23. Spread and metastasis-
Local spread
Lymph nodes-15% cases
Distant metastasis- lungs, liver and peritoneum.

24. Rhabdomyosarcoma:-
Rhabdomyosrcoma is the most common soft tissue
sarcoma of childhood & adolescence, usually appear
before age 20 year.
Types:-
Embryonal (most common)
Alveolar Rhabdomyosarcoma
Pleomorphic (least common)

25. Morphology:-
Pleomorphic Rhabdomyosarcoma:- It is least
common.
Site:- Extremities & thigh.
Age:- Adult
Grossly :- It is confined within fascial compartment
& have the shape of muscle from which it arises.

26. Microscopically:-Pleomorphic type
Tumor is
pleomorphic with
giant cells.

27. Embryonal rhabdomyosarcoma
Clinical Feature:-Arise from unsegmented &
undifferentiated mesoderm.
Site:- Common in head & neck region
Orbit
Nasopharynx
Bile duct
Urogenital tract
Age :- 3 -12 years, can occur in adults also.
Grossly-poorly circumscribed, white,soft.

28. Embryonal
rhabdomyosarcoma
composed
predominantly of round
cells.
There is perivascular
pseudorosette around
blood vessels.

29. Microscopically(Embryonal type)
Tumor cells
are small &
spindle
shaped.
Oval
eccentric
nuclei
acidophilic
cytoplasm.

30. Botryoid type
When beneath a mucosal
membrane , such as vagina,
urinary bladder or nasal
cavity it frequently form
large polypoid mass
resembling a bunch of
grapes- Hence name
“Sarcoma Botryoides”
Dense zone of
undifferentiated tumor cells
immediately beneath the
epithelium , aformation of
known as Nicholson’s
Cambium Layer.

31. Alveolar rhabdomyosarcoma
Common Site:- Forearm
Arm
Perirectal & perianal region
Head and neck region.
Age- 10-25 yrs.

32. Alveolar type

33. Microscopically( alveolar type)
Tumor cells are
small,round are
sepearted in nest by
connective tissue septa

35. Special techniques-
Special Stains:-
PTAH
Masson’s trichome
Silver impregnation technique
Immunohistochemically:- Markers are
Myogenin
Desmin
Sarcomeric actin
Myosin
Myoglobin

36. Tropomyosin a actinin,titin, Z protein
Vimentin
Enzymes( creatine kinase)
Neurofilament & S-100 protein
CARP- cardiac ankyrin related protein

37. EWINGS SARCOMA
Ewing’s sarcoma limited neural differentiation.
PNET show more neural features.
Age:- 5 to 20 years (commonly)
Infancy or adulthood rarely
Sex:- Male predilection.
It generally arise in medullary cavity of shaft from
which it permeate the cortex & invade the soft
tissue.

38. EWINGS SARCOMACommon site- Long bones( femur,tibia,
humerus,fibula).
Rare site- Bone of pelvis, rib , vertebra, mandible,
clavicle.
Clinical features:
Pain
Fever
Leuckocytosis

39. Genetic Predisposition:-
Over 95% show reciprocal translocation of
chromosome 11 : 22 (q24 : q 12).
This leads to fusion of EWS gene with FLI-1.

40. This tranlocation can be detected by RT-PCR.
This can be used for the detection of primary and
metastatic or residual disease in tissue & body fluids
including blood.
The EWS rearrangement has also been detected by
FISH technique.

41. Radiograph:-
Ewing’s sarcoma of
fibula.
Onion skin appearance

42. Gross-

43. Microscopically:-

45. Histochemically:-

46. Immunohistochemically:-
Positive for Vimentin.
Neuron specific enolase
Neurofilament
Leu 7
CD -99

47. Medulloblastoma
 5-10 yrs.
Site:- Commonly arise from Cerebellum.
Rapid growth may occlude the flow of CSF leading to
hydrocephalous.

48. The tumor - circumscribed, gray & friable.
 microscopic - extremely cellular.
 small cells with scanty cytoplasm & hyperchromatic
nuclei that frequently crescent shaped.
Abundant mitosis.

49. Variants of medulloblastoma:-
- Classical Medulloblastoma
- Desmoplastic Medulloblastoma
- Neuroblastic medulloblastoma
- Anaplastic Medulloblastoma

50. Medulloblastoma

52. Desmoplastic
medulloblastoma
:-Micronodular zone of
reduced cellularity( “
pale island”)

53. “Neuroblastic “
medulloblastoma.
This variant of
medulloblastoma is
typified by the linear
streaming of rounded,
‘neurocytic’ tumor cell
nuclei within amassed
cytoplasmic processes

54. Large cell/anaplastic
medulloblastoma.
Showing prominent
nucleoli &
pronunced mitotic &
apoptotic activity .

55. LYMPHOMA(Chronic lymphocytic leukemia/small
lymphocytic lymphoma
Age:- median age is 60 years.
Sex ratio:- 2:1 male to female
Clinical feature:- Mostly asymptomatic

56. Morphology:-
SLL/CLL:- Low power
view show diffuse
effacement of nodal
architecture.

58. -1.with absolute lymphocytosis.
2.associated with monoclonal gammopathy
3. hypogammaglobulinemia
10-15% cases – autoimmune hemolytic anemia.
May transform into diffuse large B cell lymphoma-
richter transformation.
IHC- CD20,CD23,CD5, .

59. RETINOBLASTOMA
Retinoblastoma is the
most common intraocular
neoplasm of children- 16
mths- 2 yrs.
It characteristically
present as a LEUKOCORIA
/ strabisumus .
Bilateral in 30% > 90%
familial cases.
Trilateral retinoblastoma

60. Genetic:- congenital.
Sporadiac – 60%
Familial – 40%
Autosomal dominant
Gene located on Chromosome –
13q14( retinoblastoma Rb gene)

61. Knudsons 2 hit hypothesis-
Genetic mutation in both allele are necessary to
produce retinoblastoma.
Hereditary retinoblastoma – somatic Mutation in
second allele.
Sporadic retinoblastoma – both mutations are
somatic.

62. GROSS:-flat or elevated
Endophytic type:- This is protrude into vitrous.
Exophytic type:-They may grow between retina &
pigmented epithelium.

63. Microscopic:-

64. Retinoblastoma with typical “ Flexner – wintersteiner rosettes”.

66. Prognosis-
Invasion of optic nerve.
Invasion of uveal tract.
Invasion of meninges.
IHC- NSE,GFAP,S-100 protein retinal binding
protein, retinal S antigen.
Long term survivors- osteosarcoma,
rhabdomyosarcoma.

67. THANK YOU