Ewing’s Sarcoma
Ewing’s Sarcoma
Soekimin, Reno Keumalazia Kamarlis
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Sumatera Utara, Medan
Abstract: It was reported a teenager, aged 16 years old with adnexal tumor, with a chief
complain of pelvic cavity enlargement and pain. Diagnose was made by histopathologic
examination. Histopathologic features showed proliferation of small-cell, round, and some
spheroidal and uniform cells. The nuclei are round or slightly oval, have finely dispersed
chromatin, some of them with vesicular nuclei and one or two distinct nucleoli. The tumor cells
have clear cytoplasm without defined cytoplasm. Clusters of tumor cells separated by fibrous
septa. Mitotic activity is variable There are proliferation of blood vessel without angioinvasion.
Keywords: ewing’s sarcoma, small-cell, round, and some spheroidal and uniform cells, fibrous
septa
Abstrak: Dilaporkan satu kasus, seorang gadis, usia 16 tahun, dengan diagnosa tumor adneksa,
dengan keluhan utama adanya massa pada rongga pelvik dan nyeri. Berdasarkan pemeriksaan
histopatologi didapatkan gambaran proliferasi sel-sel berukuran kecil, bentuk bulat dan sferoid,
uniform. Inti bulat – oval, kromatin tersebar merata, beberapa diantaranya dengan inti vesikuler
dengan satu dua anak inti, sitoplasma jernih dengan batas tidak jelas. Kelompokan sel-sel tumor
dibatasi oleh sekat-sekat jaringan ikat. Gambaran mitosis dapat dijumpai. Tampak proliferasi
pembuluh darah dan tidak dijumpai angioinvasi.
Kata kunci: ewing’s sarcoma, sel-sel bentuk bulat, sferoid dan uniform, septa jaringan ikat
INTRODUCTION
Ewing’s sarcoma is a small-cell malignant
neoplasm of bone which develops in the
diaphysis or metaphysis of long bones, most
often the femur, tibia and humerus, as well as
in the pelvis (pelvic girdle, and illium). In this
case, the patient suffered with enlarge
abdominal and pain for two month. She
consulted to the gynecologist and from USG
examination the was big mass in pelvic cavity.
Intra operation finding the was a mass at the
1
pelvic bone.
From the biopsy, the specimen shows a
Ewing’s sarcoma with proliferation of smallcell, round, and some spheroidal and uniform
cells. . The tumor cells have clear cytoplasm
with-out well-defined cytoplasm and island of
tumor cells separated by fibrous septa. There
are proliferation of blood vessel and interstitial
bleeding features. Mitotic activity is
1,2,3
variable.
CASE REPORT
A teenager, aged 16 years old with
adnexal tumor, with a chief complain of
pelvic cavity enlargement and pain. Diagnose
was made by histopathologic examination.
From gross finding
specimen from mass
pelvic biopsy, fragmented, volume about 5 cc,
pale yellow colored and elastic.
Microscopic features, the preparation
contained of proliferation of small-cell, round,
and some spheroidal and uniform cells. The
nuclei are round or slightly oval, have finely
dispersed chromatin, some of them with
vesicular nuclei and one or two indistinct
nucleoli. The tumor cells have clear cytoplasm
without defined cytoplasm. Clusters of tumor
cells separated by fibrous septa. Mitotic
activity is variable There are proliferation of
blood vessel without angioinvasion.
RESUME
Tend to Ewing’s sarcoma
Majalah Kedokteran Nusantara Volume 41 y No. 3 y September 2008
219
Laporan Kasus
Figure 1. Clusters of small-cell, round and uniform,
separated by fibrous septa
Figure 2. The nuclei are round and oval, dispered
chromatin, clear and indistinct cytoplasm
DISCUSSION
Ewing’s sarcoma classically presents as
pain,
often
accompanied
by
local
inflammation. Fever is fairly common and
may initially suggest the possibility of
1,2
inflammatory lesion.
There is definite male predilection.
Children and adolescents are usually affected,
a younger population than with any other
primary bone tumor. About 75 percent of the
patients with Ewing’s sarcoma are in the first
two decades of life. The youngest patients was
5 months old and about 9 percent were in the
2,3
first 5 years of life.
Patients present with pain, with or
without swelling. Pathologic fracture is rare.
Some patients present with fever associated
with
laboratory
findings
of
anemia,
leucocytyosis, and increased erythrocyte
sedimentation rate, all of which suggest
1,2,3,4,5
infection.
Gross finding, Ewing’s sarcoma tumor is
a soft, white (fish-flesh) mass of almost liquid
consistency. When tumor is sectioned, the
contents may run like pus, and this may lead
to a mistaken diagnosis of osteomyelitis.
Geographic or punctate areas of necrosis may
220
be prominent. The cortex is often thickened,
and fleshy tumor is seen between layers of
thickened periosteum. In the modern era,
almost all patients receive preoperative
chemotherapy, radiotherapy, or both before
surgical resection. In a resected specimen, the
area of the tumor may be fibrotic or scarred.
Occationally, the area is cystic, containing
2,4
liquid necrotic debris.
From cytologic findings, fine-needle
aspiration biopsy (FNAB) specimens of
primary Ewing’s sarcoma/PNET of bone are
typically highly cellular. Two main types can
be recognized in classics cases of Ewing’s
sarcoma. The predominant population
consists of relatively uniform cells with sparse,
poorly defined cytoplasm and rounded,
uniform nucleoli containing finely dispered
chromatin and inconspicuous nucleoli. Less
frequent are scattered, smaller cells, with
hyperchromatic, dense nuclei. In addition,
occasional cells with abundant glycogen and
finely vacuolated cytoplasm are seen.
Atypical
variants
of
Ewing’s
sarcoma/PNET have a uniform population of
somewhat larger cells with more-developed
cytoplasm, enlarged nuclei with more
irregular chromatin, and clearly discernable
nucleoli. In these cases, mitotic figures are
often
seen.
Although
rossette-like
arrangements of tumor cells have been
described in aspirates of PNET, its distinction
from classic Ewing’s sarcoma is usually
3,5,6,7
impossible with FNA cytology.
Histopathology findings, the essential
microscopic finding is proliferation of smallcell, round, uniform cells and no matrix
production. The Intergroup Ewing’s Sarcoma
Study divided the growth pattern of this
tumor into three types based on histologic
findings: 1) diffuse: broad fields of tumor
without topographic features; 2) lobular:
island of tumor cells separated by fibrous
septa; 3) filagree: delicate bicellular
anastomosing
strands
separated
by
fibrovascular stroma.
Ewing’s sarcoma most often grows in a
diffuse or sheet-like pattern in the bone
marrow and may assume lobular and filagree
patterns when it invades soft tissue. The
tumor cells have clear cytoplasm with-out
well-defined cytoplasm boundaries, creating
the impressions of a sea of cytoplasm
Majalah Kedokteran Nusantara Volume 41 y No. 3 y September 2008
Soekimin dkk.
peppered with almost uniformly placed
nuclei. The cytoplasm contains a moderate to
8
large amount of glycogen granules. The nuclei
have finely dispersed chromatin and one or
two indistinct nucleoli. Mitotic activity is
variable.
Necrosis may be slight or extensive;
viable tumor may be arranged perivascular
pattern. Nuclear dust may encrust vessels,
producing the Azzopardi phenomenon that,
best known with small cell carcinoma of the
lung.
Since the original description by Ewing, it
has been recognized that the tumor may
contain rossettes, which is a feature
considered typical of primitive neural tumors.
Indeed, a small subset of Ewing’s sarcoma has
a lobulated growth pattern, prominent
rossettes, and even a fibrillary background,
features that strongly suggest neural
primitive
differentiation.
The
term
neuronectodermal tumor (PNET) has been
applied to this lesion. Immunohistochemical
and cytogenetic studies have confirmed that
Ewing’s
sarcoma
may
derived
from
neuroectoderm and that classic Ewing’s
sarcoma, large cell Ewing’s sarcoma, and
PNET (including the so-called Askin’s tumor)
all belong to the same family but have
7
different degrees of formation.
Histologic grading is not practical
because of the uniform appearance from
tumor to tumor. All small celll sarcomas are
high-grade tumors (grade 4 of 4).
Open biopsies are rarely necessary to
confirm the diagnosis of Ewing’s sarcoma. If
the findings on fine-needle aspiration cytology
are not diagnostic, open biopsy performed and
frozen section must be examined to confirm
the presence of viable tumor and to allocate
1,2,4,5,9
material for all special studies.
CONCLUSION
We report a rare case, young female, with
enlarge abdominal and from biopsy result
diagnosed as Ewing’s sarcoma. From
microscopic findings shows proliferation of
small-cell, round, and some spheroidal and
uniform cells. The nuclei are round or slightly
oval, have finely dispersed chromatin, some of
them with vesicular nuclei and one or two
indistinct nucleoli. The tumor cells have clear
Ewing’s Sarcoma...
cytoplasm without defined cytoplasm.
Clusters of tumor cells separated by fibrous
septa. Mitotic activity is variable There are
proliferation of blood vessel without
angioinvasion.
Unfortunately, we didn’t find result of
laboratory examination to confirm clinical
features. To make sure, it’s better to make
special stain (Periodic Acid Schiff and
reticulin) to differ with malignant lymphoma
and immunohistochemistry (CD99, vimentin,
NSE, and S-100 protein).
The microscopic differential diagnosis of
Ewing’s sarcoma includes osteomyelitis,
eosinophilic granuloma, and the group of
small-cell tumors that includes lymphoma,
leukemia, and metastatic neuroblastoma (and,
in the case of soft-tissue Ewing’s sarcoma).
REFERENCES
1. Bullough Peter, Orthopedic Pathology,
fourth edition, Mosby, 2004, p. 471-4.
th
2.
Robbins et all, Basic Pathology, 7
edition, Saunders, 2003, p. 770-2.
3.
Mills Stacey et all, Stenberg’s Diagnostic
th
Surgical Pathology, volume IA, 4
edition, Lippincott Williams & Wilkins,
2004, p. 272-3.
4.
Krishnan, et all, Tumors of The Bones
and Joints 2, AFIP Atlas of Tumor
Pathology series 4, ARP, 2005, p. 20922.
5.
Rosai, Rosai and Ackerman’s Surgical
Pathology, volume two, ninth edition,
Mosby, 2004, p.2172-7.
6.
Orel, Svante R et all, Fine Needle
Aspiration Cytology, fourth edition,
Elsevier, 2005, p. 442-3.
7.
Fine-needle Aspiration Cytology of
Extraskeletal Ewing’s sarcoma, available
at
http:///www.javascript:AL_get(this,’jour’
Diagn Cytopathol.’)
8.
Kissane, John M, Anderson’s Pathology,
th
volume II, 9 edition, Mosby, 1990, p.
2045-47.
9.
What is Ewing’s Sarcoma, available at:
http://www.cancer.org/docroot/NWS/N
WS_O.asp
Majalah Kedokteran Nusantara Volume 41 y No. 3 y September 2008
221
Soekimin, Reno Keumalazia Kamarlis
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Sumatera Utara, Medan
Abstract: It was reported a teenager, aged 16 years old with adnexal tumor, with a chief
complain of pelvic cavity enlargement and pain. Diagnose was made by histopathologic
examination. Histopathologic features showed proliferation of small-cell, round, and some
spheroidal and uniform cells. The nuclei are round or slightly oval, have finely dispersed
chromatin, some of them with vesicular nuclei and one or two distinct nucleoli. The tumor cells
have clear cytoplasm without defined cytoplasm. Clusters of tumor cells separated by fibrous
septa. Mitotic activity is variable There are proliferation of blood vessel without angioinvasion.
Keywords: ewing’s sarcoma, small-cell, round, and some spheroidal and uniform cells, fibrous
septa
Abstrak: Dilaporkan satu kasus, seorang gadis, usia 16 tahun, dengan diagnosa tumor adneksa,
dengan keluhan utama adanya massa pada rongga pelvik dan nyeri. Berdasarkan pemeriksaan
histopatologi didapatkan gambaran proliferasi sel-sel berukuran kecil, bentuk bulat dan sferoid,
uniform. Inti bulat – oval, kromatin tersebar merata, beberapa diantaranya dengan inti vesikuler
dengan satu dua anak inti, sitoplasma jernih dengan batas tidak jelas. Kelompokan sel-sel tumor
dibatasi oleh sekat-sekat jaringan ikat. Gambaran mitosis dapat dijumpai. Tampak proliferasi
pembuluh darah dan tidak dijumpai angioinvasi.
Kata kunci: ewing’s sarcoma, sel-sel bentuk bulat, sferoid dan uniform, septa jaringan ikat
INTRODUCTION
Ewing’s sarcoma is a small-cell malignant
neoplasm of bone which develops in the
diaphysis or metaphysis of long bones, most
often the femur, tibia and humerus, as well as
in the pelvis (pelvic girdle, and illium). In this
case, the patient suffered with enlarge
abdominal and pain for two month. She
consulted to the gynecologist and from USG
examination the was big mass in pelvic cavity.
Intra operation finding the was a mass at the
1
pelvic bone.
From the biopsy, the specimen shows a
Ewing’s sarcoma with proliferation of smallcell, round, and some spheroidal and uniform
cells. . The tumor cells have clear cytoplasm
with-out well-defined cytoplasm and island of
tumor cells separated by fibrous septa. There
are proliferation of blood vessel and interstitial
bleeding features. Mitotic activity is
1,2,3
variable.
CASE REPORT
A teenager, aged 16 years old with
adnexal tumor, with a chief complain of
pelvic cavity enlargement and pain. Diagnose
was made by histopathologic examination.
From gross finding
specimen from mass
pelvic biopsy, fragmented, volume about 5 cc,
pale yellow colored and elastic.
Microscopic features, the preparation
contained of proliferation of small-cell, round,
and some spheroidal and uniform cells. The
nuclei are round or slightly oval, have finely
dispersed chromatin, some of them with
vesicular nuclei and one or two indistinct
nucleoli. The tumor cells have clear cytoplasm
without defined cytoplasm. Clusters of tumor
cells separated by fibrous septa. Mitotic
activity is variable There are proliferation of
blood vessel without angioinvasion.
RESUME
Tend to Ewing’s sarcoma
Majalah Kedokteran Nusantara Volume 41 y No. 3 y September 2008
219
Laporan Kasus
Figure 1. Clusters of small-cell, round and uniform,
separated by fibrous septa
Figure 2. The nuclei are round and oval, dispered
chromatin, clear and indistinct cytoplasm
DISCUSSION
Ewing’s sarcoma classically presents as
pain,
often
accompanied
by
local
inflammation. Fever is fairly common and
may initially suggest the possibility of
1,2
inflammatory lesion.
There is definite male predilection.
Children and adolescents are usually affected,
a younger population than with any other
primary bone tumor. About 75 percent of the
patients with Ewing’s sarcoma are in the first
two decades of life. The youngest patients was
5 months old and about 9 percent were in the
2,3
first 5 years of life.
Patients present with pain, with or
without swelling. Pathologic fracture is rare.
Some patients present with fever associated
with
laboratory
findings
of
anemia,
leucocytyosis, and increased erythrocyte
sedimentation rate, all of which suggest
1,2,3,4,5
infection.
Gross finding, Ewing’s sarcoma tumor is
a soft, white (fish-flesh) mass of almost liquid
consistency. When tumor is sectioned, the
contents may run like pus, and this may lead
to a mistaken diagnosis of osteomyelitis.
Geographic or punctate areas of necrosis may
220
be prominent. The cortex is often thickened,
and fleshy tumor is seen between layers of
thickened periosteum. In the modern era,
almost all patients receive preoperative
chemotherapy, radiotherapy, or both before
surgical resection. In a resected specimen, the
area of the tumor may be fibrotic or scarred.
Occationally, the area is cystic, containing
2,4
liquid necrotic debris.
From cytologic findings, fine-needle
aspiration biopsy (FNAB) specimens of
primary Ewing’s sarcoma/PNET of bone are
typically highly cellular. Two main types can
be recognized in classics cases of Ewing’s
sarcoma. The predominant population
consists of relatively uniform cells with sparse,
poorly defined cytoplasm and rounded,
uniform nucleoli containing finely dispered
chromatin and inconspicuous nucleoli. Less
frequent are scattered, smaller cells, with
hyperchromatic, dense nuclei. In addition,
occasional cells with abundant glycogen and
finely vacuolated cytoplasm are seen.
Atypical
variants
of
Ewing’s
sarcoma/PNET have a uniform population of
somewhat larger cells with more-developed
cytoplasm, enlarged nuclei with more
irregular chromatin, and clearly discernable
nucleoli. In these cases, mitotic figures are
often
seen.
Although
rossette-like
arrangements of tumor cells have been
described in aspirates of PNET, its distinction
from classic Ewing’s sarcoma is usually
3,5,6,7
impossible with FNA cytology.
Histopathology findings, the essential
microscopic finding is proliferation of smallcell, round, uniform cells and no matrix
production. The Intergroup Ewing’s Sarcoma
Study divided the growth pattern of this
tumor into three types based on histologic
findings: 1) diffuse: broad fields of tumor
without topographic features; 2) lobular:
island of tumor cells separated by fibrous
septa; 3) filagree: delicate bicellular
anastomosing
strands
separated
by
fibrovascular stroma.
Ewing’s sarcoma most often grows in a
diffuse or sheet-like pattern in the bone
marrow and may assume lobular and filagree
patterns when it invades soft tissue. The
tumor cells have clear cytoplasm with-out
well-defined cytoplasm boundaries, creating
the impressions of a sea of cytoplasm
Majalah Kedokteran Nusantara Volume 41 y No. 3 y September 2008
Soekimin dkk.
peppered with almost uniformly placed
nuclei. The cytoplasm contains a moderate to
8
large amount of glycogen granules. The nuclei
have finely dispersed chromatin and one or
two indistinct nucleoli. Mitotic activity is
variable.
Necrosis may be slight or extensive;
viable tumor may be arranged perivascular
pattern. Nuclear dust may encrust vessels,
producing the Azzopardi phenomenon that,
best known with small cell carcinoma of the
lung.
Since the original description by Ewing, it
has been recognized that the tumor may
contain rossettes, which is a feature
considered typical of primitive neural tumors.
Indeed, a small subset of Ewing’s sarcoma has
a lobulated growth pattern, prominent
rossettes, and even a fibrillary background,
features that strongly suggest neural
primitive
differentiation.
The
term
neuronectodermal tumor (PNET) has been
applied to this lesion. Immunohistochemical
and cytogenetic studies have confirmed that
Ewing’s
sarcoma
may
derived
from
neuroectoderm and that classic Ewing’s
sarcoma, large cell Ewing’s sarcoma, and
PNET (including the so-called Askin’s tumor)
all belong to the same family but have
7
different degrees of formation.
Histologic grading is not practical
because of the uniform appearance from
tumor to tumor. All small celll sarcomas are
high-grade tumors (grade 4 of 4).
Open biopsies are rarely necessary to
confirm the diagnosis of Ewing’s sarcoma. If
the findings on fine-needle aspiration cytology
are not diagnostic, open biopsy performed and
frozen section must be examined to confirm
the presence of viable tumor and to allocate
1,2,4,5,9
material for all special studies.
CONCLUSION
We report a rare case, young female, with
enlarge abdominal and from biopsy result
diagnosed as Ewing’s sarcoma. From
microscopic findings shows proliferation of
small-cell, round, and some spheroidal and
uniform cells. The nuclei are round or slightly
oval, have finely dispersed chromatin, some of
them with vesicular nuclei and one or two
indistinct nucleoli. The tumor cells have clear
Ewing’s Sarcoma...
cytoplasm without defined cytoplasm.
Clusters of tumor cells separated by fibrous
septa. Mitotic activity is variable There are
proliferation of blood vessel without
angioinvasion.
Unfortunately, we didn’t find result of
laboratory examination to confirm clinical
features. To make sure, it’s better to make
special stain (Periodic Acid Schiff and
reticulin) to differ with malignant lymphoma
and immunohistochemistry (CD99, vimentin,
NSE, and S-100 protein).
The microscopic differential diagnosis of
Ewing’s sarcoma includes osteomyelitis,
eosinophilic granuloma, and the group of
small-cell tumors that includes lymphoma,
leukemia, and metastatic neuroblastoma (and,
in the case of soft-tissue Ewing’s sarcoma).
REFERENCES
1. Bullough Peter, Orthopedic Pathology,
fourth edition, Mosby, 2004, p. 471-4.
th
2.
Robbins et all, Basic Pathology, 7
edition, Saunders, 2003, p. 770-2.
3.
Mills Stacey et all, Stenberg’s Diagnostic
th
Surgical Pathology, volume IA, 4
edition, Lippincott Williams & Wilkins,
2004, p. 272-3.
4.
Krishnan, et all, Tumors of The Bones
and Joints 2, AFIP Atlas of Tumor
Pathology series 4, ARP, 2005, p. 20922.
5.
Rosai, Rosai and Ackerman’s Surgical
Pathology, volume two, ninth edition,
Mosby, 2004, p.2172-7.
6.
Orel, Svante R et all, Fine Needle
Aspiration Cytology, fourth edition,
Elsevier, 2005, p. 442-3.
7.
Fine-needle Aspiration Cytology of
Extraskeletal Ewing’s sarcoma, available
at
http:///www.javascript:AL_get(this,’jour’
Diagn Cytopathol.’)
8.
Kissane, John M, Anderson’s Pathology,
th
volume II, 9 edition, Mosby, 1990, p.
2045-47.
9.
What is Ewing’s Sarcoma, available at:
http://www.cancer.org/docroot/NWS/N
WS_O.asp
Majalah Kedokteran Nusantara Volume 41 y No. 3 y September 2008
221