Small round cell_tumor_DR NARMADA

Moderator:-Dr. Poonam Nanwani

Speaker:- Dr. Narmada Prasad Tiwari

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.

The differential diagnosis of such tumors are:-

NeuroblastomaWilms tumour(Nephroblastoma)RhabdomyosarcomaEwing’s sarcoma/PNETMedulloblastomaRetinoblastomaLymphoma

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

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

Gross-

Neuorblastoma MorphologySmall round blue cell tumor

neuorpil formation (fibers, i.e., axons dendrites, mostly unmyelinated)

rosette formationimmunochemistry – neuron specific enolaseEM – secretory granules (catecholamine)

Usual features of anaplasiahigh mitotic rate is unfavorableevidence of Schwann cell or ganglion

differentiation favorable

Histologically

Undifferentiated type

Differentiating type Poorly differentiated type

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

Prognostic factors in neuroblastomaVariable 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.

WILMS’ TUMOR(NEPHROBLASTOMA)

Age:- 3 -6 yearsSex:- No sex predelictionClinical features-Large abdominal massHematuriaPain in abdomenHypertension

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’ tumorAniridiaGenital anomaliesRetardation

Beckwith wiedemann Syndrome:-OmphaloceleMacroglossiaHemihypertrophy of organs

Denys Drash Syndrome:-Gonadal dysgenesis( male

psuedohermaphroditism)Early onset nephropathy

Gross:- solid, well circumscribed.On cut-:-solid & pale gray & often exhibit

areas of cystic changes, necrosis & hemorrhage.

Microscopically :- Three major component are identified.

I- Undifferentiated blastemaII – Mesenchymal ( stromal) tissueIII – 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.

Additional morphological features-Ciliated,mucinous, squamous or transitional

epithelium, neuroepithelium,mature adipose tissue,Cartilage & bone

Anaplastic wilms tumour

Spread and metastasis-Local spreadLymph nodes-15% casesDistant metastasis- lungs, liver and

peritoneum.

Rhabdomyosarcoma:-Rhabdomyosrcoma is the most common soft

tissue sarcoma of childhood & adolescence, usually appear before age 20 year.

Types:-Embryonal (most common)Alveolar RhabdomyosarcomaPleomorphic (least common)

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.

Microscopically:-Pleomorphic type

Tumor is pleomorphic with giant cells.

Embryonal rhabdomyosarcomaClinical Feature:-Arise from unsegmented

& undifferentiated mesoderm.Site:- Common in head & neck regionOrbitNasopharynxBile ductUrogenital tract

Age :- 3 -12 years, can occur in adults also.Grossly-poorly circumscribed, white,soft.

Embryonal rhabdomyosarcoma composed predominantly of round cells.

There is perivascular pseudorosette around blood vessels.

Microscopically(Embryonal type) Tumor

cells are small & spindle shaped.

Oval eccentric nuclei

acidophilic cytoplasm.

Botryoid typeWhen 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.

Alveolar rhabdomyosarcomaCommon Site:- ForearmArmPerirectal & perianal regionHead and neck region.Age- 10-25 yrs.

Alveolar type

Microscopically( alveolar type)Tumor cells are

small,round are sepearted in nest by connective tissue septa

Special techniques-

Special Stains:- PTAHMasson’s trichomeSilver impregnation techniqueImmunohistochemically:- Markers areMyogeninDesminSarcomeric actinMyosinMyoglobin

Tropomyosin a actinin,titin, Z proteinVimentinEnzymes( creatine kinase)Neurofilament & S-100 proteinCARP- cardiac ankyrin related protein

EWINGS SARCOMAEwing’s sarcoma limited neural

differentiation. PNET show more neural features.

Age:- 5 to 20 years (commonly) Infancy or adulthood rarelySex:- Male predilection. It generally arise in medullary cavity of shaft

from which it permeate the cortex & invade the soft tissue.

EWINGS SARCOMACommon site- Long bones( femur,tibia,

humerus,fibula).Rare site- Bone of pelvis, rib , vertebra,

mandible, clavicle.Clinical features:PainFeverLeuckocytosis

Genetic Predisposition:-Over 95% show reciprocal translocation of

chromosome 11 : 22 (q24 : q 12).

This leads to fusion of EWS gene with FLI-1.

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.

Radiograph:-

Ewing’s sarcoma of fibula.

Onion skin appearance

Gross-

Microscopically:-

Histochemically:-

Immunohistochemically:-Positive for Vimentin.Neuron specific enolaseNeurofilamentLeu 7CD -99

Medulloblastoma 5-10 yrs.

Site:- Commonly arise from Cerebellum.

Rapid growth may occlude the flow of CSF leading to hydrocephalous.

The tumor - circumscribed, gray & friable. microscopic - extremely cellular.

small cells with scanty cytoplasm & hyperchromatic nuclei that frequently crescent shaped.

Abundant mitosis.

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

Medulloblastoma

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

“Neuroblastic “ medulloblastoma.

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

Large cell/anaplastic medulloblastoma.

Showing prominent nucleoli & pronunced mitotic & apoptotic activity .

LYMPHOMA(Chronic lymphocytic leukemia/small lymphocytic lymphomaAge:- median age is 60 years.

Sex ratio:- 2:1 male to femaleClinical feature:- Mostly asymptomatic

Morphology:-SLL/CLL:- Low

power view show diffuse effacement of nodal architecture.

-1.with absolute lymphocytosis.2.associated with monoclonal gammopathy3. hypogammaglobulinemia10-15% cases – autoimmune hemolytic

anemia.May transform into diffuse large B cell

lymphoma- richter transformation.IHC- CD20,CD23,CD5, .

RETINOBLASTOMARetinoblastoma 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

Genetic:- congenital.Sporadiac – 60%Familial – 40% Autosomal dominantGene located on Chromosome –

13q14( retinoblastoma Rb gene)

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.

GROSS:- flat or elevated

Endophytic type:- This is protrude into vitrous.Exophytic type:-They may grow between

retina & pigmented epithelium.

Microscopic:-

Retinoblastoma with typical “ Flexner – wintersteiner rosettes”.

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.

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