SMALL BLUE ROUND CELL TUMOUR, PEDIATRIC NEOPLASM,

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