ROUND CELL TUMORS

Presented by:

Dr. Kush Pathak

Contents Introduction Classification Description of individual round cell tumorsEwing’s SarcomaPrimitive neuroectodermal tumorMerkel cell carcinomaRhabdomyosarcomaSmall cell carcinomaLymphomaSmall cell osteocarcinomaMesenchymal Chondrosarcoma

Round cell liposarcomaDesmoplastic small round cell tumorSynovial Carcinoma

Introduction

The term small round cells are used to describe the

lesions in which dominant population consists of

relatively small cells with basophilic nuclei and little or

no cytoplasm.

The large round cells tumors are those which consist

relatively larger cells than typical small round cell

tumors.

These round cells tumors have several histological

pattern, immunohistochemical & electronmicroscopic

features that can help in differential diagnosis.

Classification ROUND CELL PATTERN

Diffuse round cell pattern

Ewing`s sarcoma

Primitive neuroectodermal tumor

Merkel cell carcinoma

Embryonal rhabdmyosarcoma

Small cell carcinoma

Lymphoma

Leukemic infiltrate

Septate or lobulated round cell pattern

Small round cells are divided by fibrous/fibrovascular

septate

Ewing`s sarcoma

Alveolar Rhabdomysarcoma

Alveolar/ Pseudoalveolar round cell pattern

Focal, poor cohesion of the round cell population resulting

in pseudo alveolar appearance

Alveolar Rhabdomyosarcoma

Primitive neuroectodermal tumor

Round cell pattern with Rosettes

A `rosette’ is like a flower, with the cells being arranged

radially around a central area.

Flexner’s( also called Flexner- Winterstein, true rosettes)-

contain clearly delineated empty central lumen.

e.g. Neuroblastoma

Primitive neuroectodermal tumor( PNET)

Homer Wright rosette-center has no lumen,but abundant

fibrillary material

e.g. Neuroblastoma

Round cell pattern with hemangiopericytomatous vascular pattern

Poorly differentiated synovial sarcoma

Mesenchymal chondrosarcoma

Round cell pattern with other components

Pseudo glands- Poorly differentiated synovial sarcoma

Cartilage- Mesenchymal chondrosarcoma

Primitive Neuroectodermal tumor( PNET)/ Extraskeletal

Ewing’s sarcoma

( ES)

II) According to size of round cell:

Small round cell – Squamous cell carcinoma, PNET,

Ewing’s sarcoma, melanoma, rhabdomyosarcoma,

langerhans cell disease, lymphoma, adenocarcinoma,

neuroendocrine carcinoma, merkel cell carcinoma,

olfactory neuroblastoma

Large round cell - Squamous cell carcinoma,

adenocarcinoma, melanoma, rhabdomyosarcoma,

lymphoid tumors, paraganglioma.

Neurogenic origin:

• Ewing’s sarcoma/ PNET

• Neuroblastoma

• Retinoblastoma

• Medulloblastoma

• Merkel Cell Tumor

• Paragangliomas

• Small Cell Tumor of Lung

Mesenchymal origin:

• Myogenic differentiation

Embryonal Rhabdomyosarcoma

Alveolar Rhabdomyosarcoma

• Osteoid differentiation:

Small Cell Osteosarcoma

• Chondroid differentiation:

Mesenchymal chondrosarcoma

• Adipose tissue like differentiation:

Myxoid/ Round Cell Liposarcoma

Hematolymphoid Origin

Lymphoma/ ‘Reticulum Cell Sarcoma’

Malignant soft tissue tumors of uncertain

type

Desmoplastic small Round cell tumor

Poorly differentiated synovial sarcoma

Small Blue Round cell tumor

Desmoplastic small round cell tumor

Ewing’s Sarcoma/ PNET

Neuroblastoma

Medulloblastoma

Rhabdomyosarcoma

Wilm’s Tumor

Retinoblastoma

Small cell lymphomas

Hepatoblastoma – only the anaplastic form has round blue

cells, the more common fetal and embryonal types do not

Primitive (undifferentiated) nerve cells

Retinoblastoma:

o Flexner- Wintersteiner rosettes: 1891 and 1897

o Knudson’s two hit hypothesis 1970

Medulloblastoma:

o 1973 WHO – posterior fossa PNET

Merkel cells - touch receptors 1875

Ewing’s sarcoma

o John Ewing – 1920

o Established a ‘new’ bone tumor; not a lymphoma

Age/ Gender Site

Retinoblastoma Bilateral – 13 months; unilateral-24 months; M=F

Eye…….. Long bones

Neuroblastoma 2 to 5 yrs; congenital; M:F=1.22:1

Distribution of symp ganglia: base of skull, pelvis, adr medulla

Medulloblastoma Childhood; common 3 to 8 yrs; M > F

Cerebellum

Ewing’s/ PNET Adolescents/ young adults;

M>F

Long bones, extraskeletal – upper thigh and arm, shoulder/ paravertebral, chest wall

Paraganglioma 4th to 5th decades Abdomen (85%), thorax –(12%), H&N (3%) - Carotid body, vagus, larynx

Small Cell carcinoma of Lung

4th decade and above Hemithorax, mediastinum, lymph node metastases

Merkel Cell Carcinoma 7th to 8th decade; M:F=1:4 Skin - periorbital

Clinical Features

Retinoblastoma Familial or de novo. White reflexes, strabismus; 2nd primary neoplasms in adolescence

Neuroblastoma 25% Congenital, non-specific symp, nodular swelling; cutaneous blue-red metastases, MIBG labeling; osteolytic bone lesions – skull, femur, humerusIncreased serum catecholamines, ferritin

Medulloblastoma Headaches, vomiting, visual impairment, nystagmus, muscular in coordination/ weakness, slurred speech

Ewing’s/ PNET Rapidly growing mass, 33% painful, sensory/ motor disturbance if nerves involved

Paraganglioma Multifocal , 10% familial – autosomal dominant, von Hippel Lindau disease; Painless, slowly growing, mobile , bruit (CBP); arteriography – enlarged, tortuous, vessels, displacement of bifurcation; Carney’s complex, MEN types I and II

Small Cell Carcinoma Lung

Smokers; cough, haemoptysis, dyspnoea, chest pain, loss of weight

Merkel Cell Carcinoma

Red/pink/blue nodular tumors; sun exposed surfaces; rapid invasion

Histopathology Prognosis

Retinoblastoma Round cells in true (FW) and pseudo (Homer-Wright) rosettes

90% if optic nerve uninvolved; 20 to 40% if involved; surgery and chemotherapy

Medulloblastoma Round, primitive cells, scant cytoplasm, hyperchromatic nuclei; HW rosettes

30% to 70% 5 yr survival;

Surgery, radiation, chemotherapy

Neuroblastoma sheets- round cells; lobules; no cytoplasm, deep blue cytoplasm; calcifications; HW rosette

Variable: spontaneous remission to poor prognosis;

Surgery - usually

Ewing’s/ PNET Uniform round/ ovoid nuclei; sheets or rosettes; scant cytoplasm, i/c glycogen

65-70% with chemotherapy.

Metastatic disease is 25-30%.

Paraganglioma Nests of cells – round nuclei, abundant cytoplasm, arranged in nests around vascular space (zellballen)

Good for resectable lesions; fatal if not resected 28% 5yr survival; surgery

Small cell carcinoma Lung

Small cells (< lymphocytes), scant cytoplasm, granular chromatin; sheets; EM: neurosecretory granules

5 yr survival 5% to 10%;

Radiation, chemotherapy

Merkel Cell Carcinoma

Large, closely packed round cells, min cytoplasm; nests pattern

H&N with nil node: good prognosis ~80% 5yr survival; node +ve ~20%; surgery

IHC

Retinoblastoma NSE, GFAP, (Synaptophysin) SYN, NF

Medulloblastoma NSE, GFAP, SYN, S100

Neuroblastoma CD99 & GFAP–ve; NSE, Protein gene product (PGP) 9.5, VIP, Chromogranin, SYN, weak catecholamine +ve ; NB-84

Ewing’s/ PNET NSE, GFAP, SYN, CD99, Leu-7, PGP 9.5, Chromogranin, HMB 45, NF

Paraganglioma NSE, Leu/ Met –enkephalin, somatostatin, VIP, subst P, ACTH, Calcitonin, Neurotensin

Small Cell Carcinoma of Lung

NSE, SYN, cytokeratins, EMA, chromogranin

Merkel Cell Carcinoma

NSE, SYN, Low mol wt CK (ck20); CrA, NCAM, Map2; CD99

A: Retinoblastoma

B: Medulloblastoma

C: Neuroblastoma

A B

C

PARAGANGLIOMA

SMALL CELL CARCINOMA MCC

Ewing’s Sarcoma/ PNET Ewing’s

• Age <30• Site: paravertebral

region, chest• H/P:

– Uniform, round cells– Fine chromatin– Pin-point nucleoli– Abundant glycogen– Rosettes absent

CD99 positive & CD45 negative

PNET• Age - <25• Site: U/ L extremities-

upper thighs, shoulder• H/P:

– Irregular cells– Coarse chromatin– Prominent nucleoli– Scant glycogen– HW rosettes;

sometimes FW

PNET EWING’s SARCOMA

Rhabdomyosarcoma

Most common soft tissue tumor in children

Histological classification:

Modified Horn and Enterline classification:

○ Embryonal (ERMS)

Botryoid

○ Alveolar (ARMS)

○ Pleomorphic

○ Other

Age: infants, children

Embryonal type: 8 yrs

Alveolar type: 16 yrs

M > F (1.3:1.0);

Alveolar type: M=F

Sites:

Head and neck: orbit, nasal cavity, palate, mouth,

pharynx/ nasopharynx

Trunk

Extremities

Deep-seated, rapid enlargement, symptoms sec.

to pressure effect, no bony erosion

Metastases: lung, lymph node, bone marrow,

heart, brain, pancreas, liver, kidney

Embryonal Rhabdomyosarcoma

A type having alternating loosely cellular areas with

myxoid stroma and densely cellular areas with spindle

cells, seen mainly in infants and small children.

Resemble embryogenesis of skeletal muscle

Varying degrees cellularity; Myxoid matrix

Small, undifferentiated, hyperchromatic round or spindle

cells

Rhabdomyoblasts:

Strap/ ribbon/ tadpole shaped; ‘broken-straw’ pattern

One or two nuclei; prominent nucleoli

Cross-striations

Spider cells’ – i/c glycogen – multivacuolated cells

Cartilaginous differentiation - genitourinary tract and peritoneal

Botryoid type:

A type of cancer that arises from rhabdomyoblasts which are

immature muscle cells. The tumors can occur arise from muscle

tissue almost anywhere in the body but in the Botryoid form, tends

to hollow organs with a mucosal lining such as the bladder, uterus

and vagina. Symptoms depend on size and location of the tumor.

Symptoms:

Asymptomatic

Vaginal lump

Polypoid growth Mucosal cavities

Sites: vagina  cervix  urinary bladder  nasopharynx biliary tract 

HistopathologyHypocellular with mucoid stroma, cambium layer

D/D – Pelvic neuroblastoma Burkitt Lymphoma

BOTRYOID TYPEERMS

Varying degrees cellularity; Myxoid matrix, Small, undifferentiated, hyperchromatic round or spindle cells, Rhabdomyoblasts are Strap/ ribbon/ tadpole shaped; ‘broken-straw’ pattern, One or two nuclei; prominent nucleoli

Immature muscle cells, Hypocellular with mucoid stroma, cambium layer

Alveolar Rhabdomyosarcoma

A type having dense proliferations of small round cells

among fibrous septa that form alveoli, seen mainly in

adolescents and young adults.

Ill-defined aggregates – round or oval cells

Central loss of cohesion – ‘alveolar spaces’

Dense fibrous septae.

‘solid’ type – at periphery; active stage of tumor

Clear-cell rhabdomyosarcoma

Rhabdomyoblasts uncommon

Multinucleated giant cells

ALVEOLAR RHABDOMYOSARCOMA

Dense proliferations of small round cells among fibrous septa, round or oval cells, Dense fibrous septae, Multinucleated giant cells, Rhabdomyoblasts uncommon

Special stains:

Not routinely used

Trichrome

PTAH (Phosphotungustic acid hematoxylin)

PAS

IHC:

desmin, muscle-specific actin, myoglobin, MyoD1; CD99

Prognosis:

Favourable: younger age, orbital location, small size, botryoid

type, nil lymph node metastases

Unfavourable: adults, non-orbital H&N/ abdomen, large size,

alveolar type (PAX3/FKHR), parameningeal site, lymph node

metastases

Pleomorphic Rhabdomyosarcoma A type having large cells with bizarre hyperchromatic

nuclei, seen in the skeletal muscles, usually in the limbs of

adults.

Historically, Stout first introduced pleomorphic

rhabdomyosarcoma (PRMS) into the literature in 1946 as

"classical" rhabdomyosarcoma

In 1958, Horn and Enterline outlined four subtypes of

rhabdomyosarcoma and called the classical ones

"pleomorphic rhabdomyosarcoma.“

It is an aggressive sarcoma.

Arises predominantly in the extremities of adult males with

a mean age of 49 years.

Pleomorphic rhabdomyosarcoma (classic variant; left) and diffusely positive desmin reactivity (right; A); myoglobin positivity (B); MyoD1 (nuclear, left) and fast myosin (cytoplasmic, BI) positivity (C); and myogenins myf 3 (nuclear, left) and myf4 (nuclear, BI) positivity (D).

According to Mary A Furlong (2001) et al. there are 3 morphologic

variants:

Type I or "classic PRMS" is defined morphologically by sheets of

large, atypical polygonal, pleomorphic rhabdomyoblasts (PRMB).

Type II, also termed "round cell PRMS," was composed

morphologically of these large PRMB among medium sized slightly

pleomorphic round rhabdomyoblasts.

Although one may consider this morphologic variant to have

similarities to embryonal rhabdomyosarcoma, there are several

reasons why these cases are better classified as the round cell variant

of pleomorphic rhabdomyosarcoma. These tumors are all in adults.

The round cells are larger than the round cells of embryonal

rhabdomyosarcoma, and there are more numerous and more atypical

pleomorphic rhabdomyoblasts within these tumors. 

Type 1 (classic variant) pleomorphic rhabdomyosarcoma, with sheets of atypical, bizarre, large, polygonal pleomorphic rhabdomyoblasts with abundant eosinophilic cytoplasm

Type 2 (round-cell variant) pleomorphic rhabdomyosarcoma, with scattered pleomorphic rhabdomyoblasts among a background of medium sized, slightly angulated round-to-epithelioid rhabdomyoblasts (A).

Higher magnification of this variant (B, left); note the geographic necrosis (common to all morphologic variants; B, right).

Type 3 (spindle cell variant) pleomorphic rhabdomyosarcoma, with scattered large polygonal pleomorphic rhabdomyoblasts and a spindled, storiform background of rhabdomyoblasts (A–B, left); the atypia, atypical mitoses, and bizarre giant cells are common to all variants (B, right).

Solid alveolar rhabdomyosarcoma subtype can be

distinguished from this round cell variant of PRMS by its

t(2;13) or variant t(1;13) chromosomal translocations

Type III, or spindle cell PRMS, was composed of large,

atypical pleomorphic rhabdomyoblasts with highly spindled

and often storiform backgrounds.

Histopathology

They are composed of large, atypical, polygonal

pleomorphic rhabdomyoblasts with abundant eosinophilic

cytoplasm.

These large rhabdomyoblasts are often arranged in clusters,

sheets, or scattered individual cells.

Atypical, vesicular nuclei with prominent nucleoli predominate.

The rhabdomyoblasts in the background that surround the large,

pleomorphic rhabdomyoblasts vary from round to spindled.

Immunohistochemistry

Immunohistochemical antibodies were applied to these tumors

in the early 1980s, predominantly using myoglobin, desmin,

creatinine kinase subunit M, and various actins to detect

skeletal muscle differentiation.

In 1993, fast myosin, a skeletal muscle-specific marker, was

added to the repertoire for PRMS

MyoD1 was applied in 1995

Myf4, a skeletal muscle-specific myogenin, has only been

studied on four cases of PRMS in the literature

Differential Diagnosis:

Malignant fibrous histiocytoma (MFH) - Occasionally

express both desmin and MSA. But should not express other

specific skeletal muscle markers, such as MyoD1, fast skeletal

muscle myosin, myf4, or myoglobin. 

Pleomorphic leiomyosarcoma - a myoid tumor with

desmin expression, morphologically has intersecting fascicles,

lacks the presence of large polygonal rhabdomyoblasts, and

also does not express skeletal muscle specific markers.

Small Cell Osteosarcoma

First described 1979 (Sim et al) 1.3% of osteosarcoamas Location:

Usually long bones Rarely simultaneous multiple bone involvement Pulmonary metastases – common

Symptoms: Pain Swelling Neurological symptoms due to pressure effects

X-ray: Intra-medullary lytic bone lesion; peripheral

sclerosis

Histopathology:

Round to oval cells

Nuclei

○ Varied nuclear size

○ Hyperchromatic

○ Prominent/ absent nucleoli

○ Coarse chromatin

Glycogen in cells

Multinucleated giant cells

Stroma:

○ Dense fibrous or myxoid or mixed

○ Osteoid production – ‘lace-like’ or hemangio-pericytomatous

Immunohistochemistry:

Osteonectin and osteocalcin positivity

Ultrastructural findings:

Precalcification stage seen as flocculent

extracellular material

Prognosis:

Low-grade >90% survival (5yrs)

Lung metastases ~30% survival (5yrs)

Mesenchymal Chondrosarcoma

First described 1959 – Lictenstein and Bernstein

Clinical features:Young adults – 15 to 35 yrs.Site:

○ Head and neck: orbit, dura mater, occiput○ Lower extremities: thigh○ Pleura, peritoneum

Painless, slowly enlarging masses

X-rays:Soft tissue mass with radiopaque flecks or

streaks

Pathologic findings:

Sheets of round or oval cells and nodules of

cartilage

Cells:

○ Hyperchromatic nuclei

○ Scant cytoplasm

○ Hemagiopericytomatous pattern

Blending of islands of cartilage with cellular

areas

MESENCHYMAL CHONDROSARCOMA

IHC:

+ve : S100, NSE, Leu-7, CD99

-ve : desmin, actin, cytokeratin

Prognosis:

5 year survival rate 54.6%

Early metastases – lung

Round Cell Liposarcoma

Liposarcoma : most common sarcoma among

adults

Spectrum: myxoid and round cell liposarcoma

Myxoid/ round cell types – 50%

Clinical features:

5th decade

Site: thigh, popliteal region

Histopathology:Myxoid type:

○ Low cellularity; round/ fusiform cells; lipoblasts○ Myxoid matrix – hyaluronic acid○ Haemorrhage, cartilaginous, osseous,

leiomyomatous fociRound cell type:

○ Loss of differentiation from myxoid type○ Sheets of primitive round cells

as a foci in the myxoid type or pure round cell type

○ High nuclear/cytoplasmic ratio○ No intervening myxoid stroma○ Occasional lipoblast: multi- or uni- vacuolar

cells

ROUND CELL LIPOSARCOMA

Cytogenetics and molecular studies:

Reciprocal translocation t(12;16)(q13;p11)

CHOP-TLS – 3 types fusion transcripts

○ Type II identified in myxoid/ round cell type

○ Unresponsive to adipogenic stimulation

○ Loss of contact inhibition

Prognosis:

Depends on % of round cell population

>25% RC = metastasis to lung, bone, soft tissues

and poor prognosis

Desmoplastic small round cell tumor Multiphenotypic differentiation

Malignant soft tissue tumors of uncertain type

Uncommon

Clinical features:

Age: 15 to 35 yrs; any age

M:F = 4:1

Site: abdominal or pelvic

Complaints: pain, distension and constipation

Histopathology:Nests of small round/ oval cellsCells:

○ Hyperchromatic nuclei○ Scant cytoplasm○ Few cells – paranuclear hyaline inclusion

- intermediate filament○ Rare – signet cells○ Occasional nuclear atypia

Cellular arrangement:○ Large nests – central necrosis○ Tubular○ Zellballen○ Cords

Abundant fibrous connective tissue stroma

DESMOPLASTIC SMALL ROUND CELL TUMOR

IHC:Cytokeratin and EMA ~100%Myogenic antigens

○ Desmin 90% - perinuclear dot-like staining○ MyoD1 –ve

Neural antigens:○ NSE ~82%○ Leu-7 ~49%○ CD99 ~34%○ NB84 ~50%

CA-125 +ve; a mucinous glucoprotein also seen in ovarian carcinomas and breast adenocarcinomas

Cytogenetics:

Translocation t(11;22)(p13;q12)

EWS-WT1 fusion transcript

Transcript induces PDGF – mitogenic

Poor prognosis

Wilm’s tumor Also called nephroblastoma. Is cancer of kidneys. Typically occurs in children, rarely in adults. First described by Dr. Max Wilms, german surgeon

(1867 - 1918). Malignant tumor containing metanephric blastema,

stromal and epithelial derivatives. Presence of abortive tubules and glomeruli

surrounded by spindled cell stroma is the characteristic feature.

Mesenchymal component may include cells showing rhabdomyoid differentiation. (malignancy – rhabdomyosarcomatous Wilms)

Clinical Features:• Abnormally large abdomen• Abdominal pain• Fever• Nausea and vomiting• Blood in the urine• High B.P. in some cases

Histopathology:May be separated into 2 prognostic groups based on pathological characteristics.

• Favorable – Contains well developed components mentioned above.

• Anaplastic – Contains diffuse Anaplasia (poorly developed cells)

• Malignant small round (blue) cells – 2x the size of resting lymphocyte (blastema component)

• Tubular structures/ rosettes (epithelial component)• Loose paucicellular stroma with spindle cells (stromal

component)

Synovial Sarcomaa

Uncertain histogenesis

Microscopic resemblance to developing synovium

Clinical features:

Age: 15 to 40 years

M:F = 1.2:1

Complaints:

Deep-seated swelling; pain or tenderness

Functional disturbance – poorly differentiated type

h/o trauma

Site: Lower extremities > upper extremities > head and neck

> trunk Head and neck: neck, pharynx, larynx

X-ray: Superficial bone erosion Multiple, small, spotty radiopacities

Histopathology: Histological subtypes:

○ Biphasic type: Epithelial and spindle cell morphologies

○ Monophasic type:Fibrous type, i.e. spindle cell typeEpithelial type

○ Poorly differentiated round cell type

Poorly differentiated round cell type:

3 types:

○ Large cell

○ Small round cell

○ Spindle cell

Rich vascularity; thin walled vessels

Intra-cytoplasmic hyaline inclusions

POORLY DIFFERENTIATED SYNOVIAL SARCOMA

IHC:

CK and EMA usually +ve; but –ve in round cell type

S100 +ve

CD99 +ve

CD34 –ve

Cytogenetics:

Reciprocal translocation t(X;18)(p11;q11)

SYT-SSX1/ SSX2

Poorly differntiated type associated with poor

prognosis

Differential DiagnosisEwing’s Sarcoma/ PNET

Neuroblastoma

ARMS

Urinary catecholamine

CD99 -ve

Alveolar pattern Rhabdomyoblasts MyoD1

Metastatic Small Cell Carcinoma -

Lung

Older age Radiograph – lung

involvement

Merkel Cell Carcinoma

Older age CD99 -ve

Differential DiagnosisEwing’s Sarcoma/ PNET

Differential DiagnosisEwing’s Sarcoma/ PNET

Mesenchymal Chondrosarcoma

Presence of cartilage

Absence of cartilage Dx difficult; similar IHC

Small Cell Osteosarcoma

Presence of osteoid

Similar IHC

Differential Diagnosis

Poorly Differentiated

Synovial Sarcoma

Round cells arranged around hemangio-pericytoma like vasculature

IHC similar

DSRCT Young adults; males Dense fibrous stroma Polyphenotypic

profile

Ewing’s Sarcoma/ PNET

Differential DiagnosisEwing’s Sarcoma/ PNET

Non-Hodgkin’s Lymphoma

Absence of glycogen

Lymph node involvement – rare in ES/ PNET

Differential Diagnosis

Rhabdomyoblasts Poorly differentiated angiosarcomas

Small cell carcinomas

Melanoma ES/PNET group

Rhabdomyosarcoma

PAS-diastase digestion

Melanoma Synovial Sarcoma Lymphoma

Differential DiagnosisRhabdomyosarcoma

MyoD1 Neuroectodermal tumors

Leiyomyosarcoma Melanoma Lymphoma Synovial Sarcoma Small Cell Carcinoma

The EWS gene• Location: 22q12

• EWS codes - nuclear protein; unknown function

Ewing’s Sarcoma– EWS translocation with ETS group of transcription factors

• FLI1 (11q24)

• ERG (21q22)

• ETV (7p22)

• E1AF (17q12)

– ETS group regulate expression of various genes; regulate epithelial-mesenchymal interactions; oncogenesis – can activate MMP’s

– EWS/ETS fusion transcript – telomerase activity in Ewing’s sarcoma

DSRCT WT1 – tumor supressor geneIn DSRCT – poor prognosis; fusion transcript

potent mitogen

Myxoid LiposarcomaRare fusionGood response to chemotherapy, rapid

recurrence and very primitive round cells

Extraskeletal myxoid chondrosarcoma

EWS/TEC [t(22;9)(q12;q22)]

TEC - tyrosine kinase gene family

WS/TEC transcript – oncogenic; activation

of transcription of target genes involved

in cell proliferation.

Round cell tumor of Hematolymphoid Origin

Lymphoma

Malignant neoplasms resembling stage of normal

lymphocyte differentiation

Hodgkin’s and Non-Hodgkin’s type

Primary Lymphoma of Bone

Hodgkin’s lymphoma:

○ ~100% nodal

○ Reed-Sternberg cells

Non Hodgkin’s Lymphoma:67% nodal and 33% extra nodalB cell, T cell/ NK cell neoplasms

Burkitt’s lymphoma childhood., rare- adults -Maxilla, mandible African –swelling of infected jaw -Loosing of teeth -Lymphadenopathy -Sporadic- abdominal tumors

Primary Lymphoma of bone Identified in 1939 by Parker and Jackson

Termed Reticulum Cell Lymphosarcoma by James

Ewing

Primary Lymphoma of Bone – 1963 by Ivins and Dahlin

94% NHL and 6% HL

Clinical features:Age: 2nd to 8th decadesM:F = 1.5:2.1Complaints: swelling and pain

Diagnostic criteria:

Primary bone focus

Histologic confirmation

No evidence of nodal of soft tissue involvement

at time of presentation

X-ray:

Lytic bone lesion

Periosteal reaction

osteomyelitis

Histopathology:

Non-Hodgkin's lymphoma

○ Large round cells

○ Irregular cleaved nuclei and prominent nucleoli

○ Reticulin fibers.

○ Commonest subtype is diffuse histiocytic lymphoma.

Hodgkin's lymphoma

○ plasma cells, lymphocytes, histiocytes and

eosinophils. Reed-Sternberg cells

Burkitt’s lymphoma:Histopathology: B-cell proliferation- diffuse pattern-Burkitt cells-Starry sky appearance

Immunohistochemistry:

Non Hodgkin’s lymphoma : Positive: Cyclin D1, CD5, CD43, CD20, CD45. Negative: CD23.

Hodgkin’s lymphoma:CD45-, CD30+, CD15+/- 

Burkitts lymphoma:Mature B-cells- CD 10 & surface immunoglbulinGenerally strongly express markers of B cell

differentiation (CD20, CD22, CD19) as well as CD10, and BCL6. The tumour cells are generally negative for BCL2 and TdT. The high mitotic activity of Burkitt lymphoma is confirmed by nearly 100% of the cells staining positive for Ki67.[

Causative organism:EBV, HIV

Hodgkin’s lymphoma - mixed cellularity type.

Burkitts lymphoma - medium size lymphoid cells, starry sky" appearance - due to scattered tingible body-laden macrophages.  Tumor cells possess small amount of basophilic cytoplasm. The cellular outline usually appears squared off.

Non Hodgkin’s lymphoma - Monomorphic small lymphoid cells less than twice the size of a resting lymphocyte, Abundant mitoses.Sclerosed blood vessels.Scattered epithelioid histiocytes.

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