Presented by:

Dr. Kush Pathak

Contents
Introduction Classification Description of individual round cell tumors Ewings Sarcoma Primitive neuroectodermal tumor Merkel cell carcinoma Rhabdomyosarcoma Small cell carcinoma Lymphoma Small cell osteocarcinoma Mesenchymal Chondrosarcoma

Round cell liposarcoma Desmoplastic small round cell tumor Synovial 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.

Flexners( 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 Ewings sarcoma ( ES)

II) According to size of round cell:

Small round cell Squamous cell carcinoma, PNET, Ewings 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:
Ewings 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 Ewings Sarcoma/ PNET

Neuroblastoma
Medulloblastoma Rhabdomyosarcoma

Wilms 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 Knudsons two hit hypothesis 1970

Medulloblastoma:
o 1973 WHO posterior fossa PNET

Merkel cells - touch receptors 1875 Ewings sarcoma

o John Ewing 1920 o Established a new bone tumor; not a lymphoma

Age/ Gender Retinoblastoma

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

Site
Eye.. Long bones

Neuroblastoma

2 to 5 yrs; congenital; M:F=1.22:1 Childhood; common 3 to 8 yrs; M > F Adolescents/ young adults; M>F

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

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

Medulloblastoma Ewings/ PNET Paraganglioma

4th to 5th decades

Abdomen (85%), thorax (12%), H&N (3%) - Carotid body, vagus, larynx Hemithorax, mediastinum, lymph node metastases Skin - periorbital

Small Cell carcinoma of Lung Merkel Cell Carcinoma

4th decade and above 7th to 8th decade; M:F=1:4

Clinical Features
Retinoblastoma Familial or de novo. White reflexes, strabismus; 2nd primary neoplasms in adolescence
25% Congenital, non-specific symp, nodular swelling; cutaneous blue-red metastases, MIBG labeling; osteolytic bone lesions skull, femur, humerus Increased serum catecholamines, ferritin
Headaches, vomiting, visual impairment, nystagmus, muscular in coordination/ weakness, slurred speech

Neuroblastoma

Medulloblastoma

Ewings/ PNET
Paraganglioma

Rapidly growing mass, 33% painful, sensory/ motor disturbance if nerves involved
Multifocal , 10% familial autosomal dominant, von Hippel Lindau disease; Painless, slowly growing, mobile , bruit (CBP); arteriography enlarged, tortuous,
vessels, displacement of bifurcation; Carneys complex, MEN types I and II

Small Cell Carcinoma Lung Merkel Cell Carcinoma

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

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

Histopathology Retinoblastoma
Round cells in true (FW) and pseudo (Homer-Wright) rosettes Round, primitive cells, scant cytoplasm, hyperchromatic nuclei; HW rosettes

Prognosis
90% if optic nerve uninvolved; 20 to 40% if involved; surgery and chemotherapy 30% to 70% 5 yr survival; Surgery, radiation, chemotherapy Variable: spontaneous remission to poor prognosis; Surgery - usually 65-70% with chemotherapy.

Medulloblastoma

Neuroblastoma

sheets- round cells; lobules; no cytoplasm, deep blue cytoplasm; calcifications; HW rosette Uniform round/ ovoid nuclei; sheets or rosettes; scant cytoplasm, i/c glycogen Nests of cells round nuclei, abundant cytoplasm, arranged in nests around vascular space (zellballen) Small cells (< lymphocytes), scant cytoplasm, granular chromatin; sheets; EM: neurosecretory granules Large, closely packed round cells, min cytoplasm; nests pattern

Ewings/ PNET Paraganglioma

Metastatic disease is 25-30%.

Good for resectable lesions; fatal if not resected 28% 5yr survival; surgery 5 yr survival 5% to 10%; Radiation, chemotherapy H&N with nil node: good prognosis ~80% 5yr survival; node +ve ~20%; surgery

Small cell carcinoma Lung Merkel Cell Carcinoma

IHC
Retinoblastoma NSE, GFAP, (Synaptophysin) SYN, NF

Medulloblastoma

NSE, GFAP, SYN, S100

Neuroblastoma

CD99 & GFAPve; NSE, Protein gene product (PGP) 9.5, VIP, Chromogranin, SYN, weak catecholamine +ve ; NB-84 NSE, GFAP, SYN, CD99, Leu-7, PGP 9.5,
Chromogranin, HMB 45, NF

Ewings/ PNET

Paraganglioma

NSE, Leu/ Met enkephalin, somatostatin, VIP, subst P, ACTH,

Calcitonin, Neurotensin

Small Cell Carcinoma of Lung Merkel Cell Carcinoma

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

B
A: Retinoblastoma B: Medulloblastoma C: Neuroblastoma

PARAGANGLIOMA

MCC

SMALL CELL CARCINOMA

Ewings Sarcoma/ PNET

Ewings Age <30 Site: paravertebral region, chest H/P:
Uniform, round cells Fine chromatin Pin-point nucleoli Abundant glycogen Rosettes absent

PNET Age - <25 Site: U/ L extremities- upper thighs, shoulder H/P:

Irregular cells Coarse chromatin Prominent nucleoli Scant glycogen HW rosettes; sometimes FW

CD99 positive & CD45 negative

PNET

EWINGs 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 Histopathology Hypocellular with mucoid stroma, cambium layer D/D Pelvic neuroblastoma Burkitt Lymphoma

ERMS

BOTRYOID TYPE

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

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 2 (round-cell variant) pleomorphic rhabdomyosarcoma, with scattered pleomorphic Type 1 (classic variant) pleomorphic rhabdomyoblasts among a background of rhabdomyosarcoma, with sheets of atypical, medium sized, slightly angulated round-toepithelioid rhabdomyoblasts (A).

bizarre, large, polygonal rhabdomyoblasts with eosinophilic cytoplasm

pleomorphic abundant 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 (AB, 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:

Symptoms:

Usually long bones Rarely simultaneous multiple bone involvement Pulmonary metastases common Pain Swelling Neurological symptoms due to pressure effects Intra-medullary lytic bone lesion; peripheral sclerosis

X-ray:

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 foci Round 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 cells Cells: 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

Wilms 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 type Epithelial 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 Diagnosis
Ewings Sarcoma/ PNET
Neuroblastoma

Urinary catecholamine CD99 -ve Alveolar pattern Rhabdomyoblasts MyoD1

ARMS

Differential Diagnosis
Ewings Sarcoma/ PNET

Metastatic Small Cell Carcinoma - Lung

Older age Radiograph lung involvement

Merkel Cell Carcinoma

Older age CD99 -ve

Differential Diagnosis
Ewings Sarcoma/ PNET
Mesenchymal Chondrosarcoma Small Cell Osteosarcoma

Presence of cartilage Absence of cartilage Dx difficult; similar IHC Presence of osteoid Similar IHC

Differential Diagnosis
Ewings Sarcoma/ PNET
Poorly Differentiated Synovial Sarcoma

Round cells arranged around hemangiopericytoma like vasculature IHC similar Young adults; males Dense fibrous stroma Polyphenotypic profile

DSRCT

Differential Diagnosis
Ewings Sarcoma/ PNET
Non-Hodgkins Lymphoma

Absence of glycogen Lymph node involvement rare in ES/ PNET

Differential Diagnosis
Rhabdomyosarcoma
Rhabdomyoblasts

Poorly differentiated angiosarcomas

Small cell carcinomas

Melanoma ES/PNET group

PAS-diastase digestion

Melanoma
Synovial Sarcoma Lymphoma

Differential Diagnosis
Rhabdomyosarcoma
MyoD1

Neuroectodermal tumors
Leiyomyosarcoma Melanoma

Lymphoma
Synovial Sarcoma Small Cell Carcinoma

The EWS gene

Location: 22q12 EWS codes - nuclear protein; unknown function Ewings 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 epithelialmesenchymal interactions; oncogenesis can activate MMPs
EWS/ETS fusion transcript telomerase activity in Ewings sarcoma

DSRCT WT1 tumor supressor gene In DSRCT poor prognosis; fusion transcript potent mitogen
Myxoid Liposarcoma Rare fusion Good 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
Hodgkins and Non-Hodgkins type
Primary Lymphoma of Bone Hodgkins lymphoma:
~100% nodal Reed-Sternberg cells

Non Hodgkins Lymphoma:

67% nodal and 33% extra nodal B cell, T cell/ NK cell neoplasms

Burkitts 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 decades M:F = 1.5:2.1 Complaints: 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

Burkitts lymphoma: Histopathology:

B-cell proliferation- diffuse pattern -Burkitt cellsStarry sky appearance

Immunohistochemistry: Non Hodgkins lymphoma :

Positive: Cyclin D1, CD5, CD43, CD20, CD45. Negative: CD23.

Hodgkins lymphoma:
CD45-, CD30+, CD15+/-

Burkitts lymphoma:

Mature B-cells- CD 10 & surface immunoglbulin Generally 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

Hodgkins lymphoma - mixed cellularity type.

Burkitts

- 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.

lymphoma

Non Hodgkins 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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