Original Histological diversity and clinical characteristics of Ewing

Article sarcoma family of tumors in children: A series from a tertiary

care center in South India
Priya D, Rekha V Kumar, Appaji L1, Aruna Kumari BS1, Padma M1, Prasanna Kumari
Departments of Pathology and 1Paediatric Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
Correspondence to: Dr. Rekha V Kumar, E‑mail: rekha_v_kumar@yahoo.co.in

Abstract
BACKGROUND: The Ewing sarcoma family of tumors (ESFT) are aggressive malignant tumors with small round cell morphology affecting mainly
children and adolescents. The aim of this study is to classify the histological diversity and clinical characteristics of ESFT in children from a
Tertiary Care Center in South India. MATERIALS AND METHODS: This retrospective descriptive study includes 51 cases of ES in children aged
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below 15 years. Clinical details were collected from case files. Histomorphological features were reviewed and tumors were subtyped into classic,
primitive neuroectodermal tumor (PNET) and atypical variants along with immunohistochemical markers, cytogenetics, and fluorescence in situ
hybridization (FISH). RESULTS: Fifty‑three percent were female and 47% were male with mean age of 10 years. The most common site of
hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/25/2024

involvement was skeletal involvement in 71%, followed by soft tissue involvement in 23%, and visceral involvement in 6%. Localized disease at
presentation was seen in 44%, locally advanced disease in 28%, and metastatic disease in 28%. Recurrence was documented during follow‑up
in 18% of the cases. Histomorphologically, classic type was the most common (72%) followed by PNET (20%) category and atypical variant (8%).
All cases were immunoreactive for CD99. Cytogenetic study in 12 cases showed translocation t(11;22) (q24;12) in 80% and variant translocations
such as t(3;16), t(3;11) with nonspecific numerical abnormalities in 20%. FISH was carried out for documentation of four cases with atypical
histomorphology. CONCLUSION: ESFT had wide histological variation which required confirmation by ancillary studies.
Key Words: Cytogenetics, Ewing sarcoma family of tumors, fluorescence in situ hybridization, pathology

Introduction histological heterogeneity with ancillary techniques including

immunohistochemistry, cytogenetics, and fluorescence in situ
Ewing sarcoma (ES)/primitive neuroectodermal hybridization (FISH) and the clinical characteristics of
tumor (PNET) is one of the aggressive malignant small pediatric cases from a Tertiary Care Center in South India.
round cell tumors that occur in bone, soft tissue, and
parenchyma, and the second most common tumor of Materials and Methods
bone in childhood and adolescence. This tumor was first
This retrospective descriptive study includes 51 pediatric
described by Ewing in 1921 as “diffuse endothelioma of
patients, of age range 2–14 years, treated for ES in our
bone.”[1] The soft tissue counterpart was first reported by
hospital from August 2009 to April 2014. The clinical
Angervall and Enzinger in 1975. [2] In 1979, Askin et al.
details were collected from case files. The clinical features
reported identical tumors in the thoracopulmonary region
such as age, sex, site of involvement, radiological findings,
which came to be known as Askin tumor.[3] Further work
serum lactate dehydrogenase (LDH) value, soft tissue
on the molecular characteristics revealed that both ES and
extension, metastasis, and recurrence were evaluated. The
PNET shared identical features and these were designated
paraffin blocks of all cases were retrieved. Histopathological
as “ES family of tumors” (ESFT). They represented the
features were reviewed and the diagnosis of ES was
primitive mesenchymal neoplasm with limited capacity for
confirmed. The tumors were further categorized into classic,
multidirectional differentiation. [4] Seventy–80% of cases
PNET, and atypical subtypes. Immunohistochemical (IHC)
exhibit classic Ewing morphology and up to 20% display
marker panels which included CD99, cytokeratin (CK),
atypical features including large cell, adamantinoma‑like,
synaptophysin, chromogranin, NSE, S100, desmin, and
spindle cell sarcoma‑like, sclerosing, clear cell, or vascular‑like
LCA were also reviewed [Table 1]. A diagnosis of PNET
patterns. [5] A panel of immunomarkers such as CD99,
was considered when Homer Wright rosettes were seen or
leukocyte common antigen (LCA), cytokeratin, desmin,
when any two different neural markers were positive. The
and neural markers such as neuron specific enolase (NSE),
atypical category included cases with large and pleomorphic
S100, and synaptophysin are usually used to distinguish
cells. Presence of necrosis and mitotic activity were noted in
the different tumors with small round cell morphology.
all cases. Immunohistochemistry analysis for all the above
Molecular testing is the gold standard and is recommended
markers was done on 4 µm thick sections collected on
in some of the cases with atypical features. Approximately,
silane‑coated slides by immunoperoxidase methods with
three quarters of patients have initially localized disease
respective antibodies as per manufacturers’ instructions.
and about two‑thirds survive disease‑free. [6] The advent
Antigen retrieval was achieved by the heat‑induced epitope
of multimodality treatment, which includes local control
retrieval method in Tris‑ethylenediaminetetraacetic acid
by surgery and radiotherapy and systemic control by
chemotherapy, has improved the overall survival in This is an open access article distributed under the terms of the Creative Commons
Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix,
these cases. This study was performed to analyze the tweak, and build upon the work non‑commercially, as long as the author is credited
and the new creations are licensed under the identical terms.
Access this article online
Quick Response Code: Website: For reprints contact: reprints@medknow.com
www.indianjcancer.com
DOI: How to cite this article: Priya D, Kumar RV, Appaji L,
10.4103/0019-509X.176700 Aruna Kumari BS, Padma M, Kumari P. Histological diversity
and clinical characteristics of Ewing sarcoma family of tumors in
PMID: children: A series from a tertiary care center in South India. Indian J
******* Cancer 2015;52:331-5.

© 2015 Indian Journal of Cancer | Pulished by Wolters Kluwer - Medknow 331

 Priya, et al.: Pathology of pediatric Ewing sarcoma

buffer pH 6.0 after Tris buffer wash. The endogenous
avidin‑binding activity was blocked by immersing in
skimmed milk powder. The sections were incubated in
primary antibody for 1 h 30 min. Enhancer with horse
radish peroxidase polymer (Biogenex) was used as secondary
antibody and 3’3‑diaminobenzidine as the chromogenic
substrate. Appropriate positive and negative controls were
included. IHC markers were scored as follows: No staining
or very exceptional positive cells were considered negative.
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wise comparisons. P <0.05 was considered to be statistically
significant.
Results
Clinical data
This retrospective study comprised 51 children, of whom
53% (27/51) were female and 47% (24/51) were male. The
age ranged between 2 and 14 years (mean: 10 years). The
most common site of involvement was skeletal involvement

Staining in <25% of the tumor cells was considered a in 71% (36/51), followed by soft tissue in 23% (12/51),
mildly positive immunoreaction (1+), staining in 25–50% and viscera in 6% (3/51). Parenchymal involvement included
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as moderately positive (2+), and in >50% as strongly two cases in the kidney and one case in the adrenal
positive (3+).[7] gland. The most common bones involved were the femur
For cytogenetic analysis, the fine needle aspiration biopsy and humerus, each in 11.8% (6/51) of the cases. The
material was cultured in RPMI‑1640 medium supplemented patients presented with local swelling as the most common
with fetal bovine serum and harvested, and slides were complaint followed by pain, fever, limb weakness, and
prepared and Giemsa‑Trypsin‑Giemsa banding procedure fracture. The size of the lesion varied from 1 cm to a
was followed. FISH was carried out on formalin‑fixed maximum of 17 cm. Eighty‑three percent (15/18) of the
paraffin embedded tissue. Break apart probes were used lesions in the long bones were located in the metadiaphyseal
for three cases (Vysis EWSR1 Break Apart FISH probe region.
kit) and dual fusion probe was used for one case (Cytocell Detailed clinical data were available only in 39 out of
Aquarius FLI1/EWSR1 Translocation Dual fusion probe 51 patients. Localized disease at presentation was seen in
kit). The dual fusion probe kit contained FLI1/EWSR1 44% (17/39), locally advanced disease in 28% (11/39), and
probe mix which consisted of green probes flanking the metastatic disease in 28% (11/39). Soft tissue extension
breakpoint region at the EWSR1 gene locus and red was seen in 63% (15/24) of the osseous cases, of which
probes flanking the breakpoint region at FLI1 locus. The five had metastasis and three had recurrence. The serum
Vysis EWSR1 (22q12) Break Apart Probe Kit consists LDH value at diagnosis ranged from 142 U/L to 1965
of a mixture of two FISH DNA probes. The first probe, U/L with a median value of 363 U/L. Out of 14 cases
a ~ 500 kb probe labeled in Spectrum Orange, flanks with LDH levels above the median value of 363 U/L,
the 5’ side of the EWSR1 gene and extends inward into two had recurrence and six had metastasis. The increased
intron 4. The second probe, a ~ 1100 kb probe labeled levels of LDH correlated significantly with the incidence
in Spectrum Green, flanks the 3’ side of the EWSR1 gene. of metastasis (P = 0.03). Bone marrow involvement was
The test was interpreted positive when more than 10% of seen in 10% (4/39) of the cases. Metastasis to other sites
the nuclei showed the split or fused signals. such as lung, liver, bone, and lymphnode was noted in
Data analysis 28% (11/39). Metastasis was more common in extraosseous
The data were analyzed using the statistical software, tumors (36%). Recurrence was documented in 18% of
SPSS (version 15.0; SPSS, Chicago, Illinois, USA) for the cases. The patients received multimodality treatment
Windows. The correlation between the discrete variables was which included surgery, chemotherapy, and radiotherapy in
performed using Chi‑square test and log‑rank test for pair accordance with their disease status.
Histological characteristics
Table 1: The panel of the immunohistochemical Seventy‑two percent (37/51) of cases exhibited classic
markers used morphology. Microscopically, the tumor had diffuse or
Antibody Source Pretreatment Time Dilution lobular pattern of arrangement of cells. The tumor cells
CD99 Mouse monoclonal Tris‑EDTA 1h 1:80 were small, with uniform round to oval or indented
Biogenex buffer 30 min nuclei, and fine chromatin [Figure 1a]. The cytoplasm
Pancytokeratin Mouse monoclonal Tris‑EDTA 1h 1:100 was pale, clear, and sometimes vacuolated. Some of
Biogenex buffer 30 min
the cases showed darker crushed cells. The mitotic
Synaptophysin Mouse monoclonal Tris‑EDTA 1h 1:80
Biogenex buffer 30 min activity was low (1–2/10 hpfs). The cases with necrosis
Chromogranin Mouse monoclonal Tris‑EDTA 1h 1:120 exhibited increased mitotic activity ranging from 3 to
Biogenex buffer 30 min 7/10 hpfs. All of them showed strong membranous CD99
Neuron specific Mouse monoclonal Tris‑EDTA 1h 1:150 expression [Figure 1b].
enolase Biogenex buffer 30 min
Twenty percent cases (10/51) were classified as PNET
LCA Mouse monoclonal Tris‑EDTA 1h 1:100
Biogenex buffer 30 min according to the criteria proposed by Schmidt et al.[8] A
S100 Rabbit polyclonal Tris‑EDTA 1h 1:80 diagnosis of PNET was considered when Homer Wright
Biogenex buffer 30 min rosettes were seen or when any two different neural
Desmin Mouse monoclonal Tris‑EDTA 1h 1:80 markers (NSE/synaptophysin/chromogranin/S100) were
Biogenex buffer 30 min positive. The number of rosettes seen in these cases varied
LCA=Leukocyte common antigen; EDTA=Ethylenediaminetetraacetic acid from a few to many. The rosettes had a central core of
332 Indian Journal of Cancer | July-September 2015 | Volume 52 | Issue 3
 Priya, et al.: Pathology of pediatric Ewing sarcoma
a b
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c d
Figure 1: (a) Sheets of small round cells with few crushed cells with
intervening fibrous bands characteristic of Classic Ewing sarcoma
(H and E, ×100). (b) Strong and diffuse membranous expression of CD99
in Classic Ewing sarcoma (immunohistochemical, ×100). (c) Primitive
neuroectodermal tumor with lobules of small round cells and numerous
Homer Wright rosettes (H and E, ×100). (d) Nesting pattern of pleomorphic
cells with high mitotic activity – atypical variant. (d) Inset: Nuclear
pleomorphism with multilobation seen (H and E, ×100)
neurofibrillary material, which was surrounded by cells with
wreath‑like nuclear arrangement [Figure 1c].
There were four atypical cases in this cohort, two of which
were in bone and two in soft tissue. Three of them had
large cells arranged in diffuse sheets and in nests. The
tumor cells had moderate to marked nuclear pleomorphism,
hyperchromatic nuclei, and one tumor demonstrated
multilobulated nuclei and prominent nucleoli [Figure 1d].
These cells had a moderate amount of eosinophilic
cytoplasm. Mitotic activity was quite high (>10/10 hpf)
in contrast to the classic cases. Large areas of necrosis were
seen in two of three cases.
Among the atypical cases, one case was categorized as
sclerosing variant of ES since the tumor had abundant
hyalinized matrix. The tumor cells were arranged in
trabeculae and cords with the small round cell morphology
resembling a desmoplastic small round cell tumor. CD99
positivity and WT1 negativity supported the diagnosis of
ES, which was further confirmed by FISH.
Necrosis was seen in 27.8% of cases, commonly in the
atypical variant (2/4 cases), followed by PNET (3/10) and
classical subtypes (9/37). All tumors had strong, diffuse, and
membranous expression of CD99. The expression of various
markers varied among the tumors, while synaptophysin
was expressed in 16.7% tumors, CK in 8% of cases, S100
expression was seen in 8%, and NSE expression in 10% of
the cases [Figure 2a‑d]. Desmin, LCA, and chromogranin
were not expressed in any of the tumors.
Cytogenetic analysis was done in 12 cases. The
translocation classic for ES t(11;22) (q24;12) was observed
in 80% and variant translocations such as t(3;16), t(3;11)
along with nonspecific numerical abnormalities were seen in
20% [Figure 3a]. FISH was carried out for documentation
of three cases with atypical histomorphology. Break apart
Indian Journal of Cancer | July-September 2015 | Volume 52 | Issue 3
a b
c d
Figure 2: (a) Immunohistochemical ×100 tumor cells of atypical variant
with diffuse and strong cytoplasmic expression of pancytokeratin.
(b) Immunohistochemical ×100 showing tumor cells with strong cytoplasmic
expression of neuron specific enolase. (c) Immunohistochemical ×100
showing scattered cytoplasmic expression of S100 by tumor cells.
(d) Immunohistochemical ×400 showing scattered cytoplasmic expression
of synaptophysin
probes were applied for three cases [Figure 3b] and dual
fusion probe for one case with signal positivity of 20%,
30%, 20%, and 80% of interphase nuclei, respectively.
Discussion
This series comprised pediatric patients (age below 15 years)
who were enrolled and treated in a Tertiary Care Center
in South India. There was female preponderance and
the mean age was 10 years. The most common sites
of involvement were bones of both upper and lower
extremities (appendicular skeleton). The patients presented
most often with swelling followed by pain. A few cases had
fever and weakness of limbs which is in accordance with
other studies.[9]
The evaluated prognostic factors included soft tissue
extension, metastasis, recurrence, and serum LDH value.
We noted that among 15 patients with soft tissue extension,
five had metastasis and three patients presented with
recurrence, which is higher compared to the rest of
the cohort, though not reaching statistical significance.
According to a study by Mendenhall et al., cases with
extraosseous extension often had metastasis with prognostic
significance.[10]
The serum LDH level had clinical value in predicting the
course of the disease. In our study, the values ranged from
142 U/L to 1965 U/L with a median of 363 U/L and
75% of cases with LDH value above this median had
metastasis with statistical significance (P < 0.05), in
concurrence with a previous report by Bacci et al. in 1999.[11]
The incidence of metastasis at presentation was 10%, while
it was 28.2% (11/39) throughout the disease course. Lung
8% (3/39) and bone marrow 10% (4/39) were the most
common sites of metastasis. Local recurrence was seen in
18% (7/39) of the cases.
Recurrence and metastatic rates were higher in extraosseous
sites than osseous sites (29% vs. 12% and 36% vs. 24%),
333
 Priya, et al.: Pathology of pediatric Ewing sarcoma
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a data in a previous study by Kavalar et al., [7] where
b
Figure 3: (a) Karyotyping of a patient with Ewing sarcoma shows classic
translocation with nonspecific numerical abnormalities. (b) Fluorescence in
situ hybridization with Vysis EWSR1 Break Apart Probe showing interphase
nuclei with one normal fusion signal and one split signal pattern indicating
rearrangement of one copy of EWSR1 region
respectively, in this study while Orr et al. had reported an
incidence of metastasis in 13% of extraosseous tumors.[12]
The prognosis for patients with ES/PNET had steadily
improved. About 75% of patients presented with
localized disease, and the combination of surgery and/or
radiotherapy and systemic chemotherapy leads to a cure
rate near 75% in this group. [13‑15] In our hospital, the
patients were given multimodality treatment according to
their disease status.
Histomorphologically, the classic type was the most
common followed by PNET and atypical variants, the
incidence of which is similar to a study done by Folpe
et al. [16] Llombart‑Bosch et al. reported 19.2% of cases
to be atypical.[17] All of our atypical cases showed diffuse
and strong membranous CD99 expression. One of them
had strong CK positivity. None of them were positive
for neuroectodermal immunomarkers. The differential
diagnosis that could be considered for atypical variant on
histomorphology included rhabdomyosarcoma, lymphoma,
and small cell osteosarcoma. Folpe et al. in 2005 analyzed
the importance of confirmation of atypical variants of ES by
molecular cytogenetics. Accordingly, all the atypical variants
in this study were confirmed by FISH.[16] In ESFT, 90–95%
of the tumors have a balanced translocation involving
chromosomes 11 and 22, which fuse portions of the EWS
gene on 22q12 with the FLI1 gene on 11q24, thus creating
a novel fusion gene with oncogenic properties.[18]
Though there has been much emphasis on the application
of cytogenetics for the confirmation of ES, many centers
in the developing countries still do not have this facility
334
in‑house. Thus, in these centers, immunohistochemistry
plays an important role in differentiating between the
various small blue round cell tumors. In the panel of
immunomarkers, CD99 is an important and “traditionally
used” one. In our study, all the cases showed strong
and diffuse membranous expression of CD99. Among
the other markers, the most commonly expressed were
the markers for neuroectodermal differentiation. This
included synaptophysin which was expressed in 16.7%,
NSE in 9.3%, and S100 in 7.4% of the cases. The
expression of neural markers was less compared to the
NSE and S100 were expressed in 66.6% and 25.4%,
respectively. However, the proportion of marker positivity
in ES in the present study fell within the range of
other studies. [19,20] In our cases, the expression of neural
immunomarkers did not correlate with the presence of
rosettes. Some of the cases that lacked light microscopic
evidence of neural differentiation could be identified with
these immunomarkers. Pancytokeratin expression that
was seen in 9.3% of the cases highlights the epithelial
differentiation in the Ewing family. There is a variability
in the reported positive rates by different authors which
range from 20% to 40%. [21‑23] Other markers such as
desmin and LCA were not expressed in our cases.
We had two cases involving the renal parenchyma. Primary
renal involvement is extremely rare in the pediatric age
group. Both of them exhibited classic morphology. They
need to be differentiated from blastemal predominant Wilms
tumor and other primitive renal tumors due to different
therapeutic and prognostic implications. Strong CD99
positivity and WT‑1 negativity with cytogenetics confirmed
the diagnosis of ES. One of these cases presented with
metastasis to liver, spleen, and bone which highlights the
aggressive behavior of renal ES described in a previous
study.[24]
One interesting and rare case of primary adrenal ES/
PNET was encountered in a 2‑year‑old child who had a
mass in adrenal gland with hepatomegaly. Microscopy of
adrenal tumor showed small round cells in sheets with
focal calcification and liver showed infiltration by tumor
in multiple small nests. Absence of neuropil, rosette
formation, ganglionic differentiation, and presence of strong
membranous CD99 expression favored a diagnosis of ES
which was further confirmed by the presence of t(11;22).
The tumor at this site is prone to recur and metastasize as
described by Komatsu et al. in 2006.[25] This case presented
with metastasis which reflected the aggressive nature of the
lesion at this site.
Conclusion
In our study, the analysis of histological heterogeneity of
ESFT emphasizes the vital role of immunohistochemistry,
cytogenetics, and FISH in supporting its diagnosis.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Indian Journal of Cancer | July-September 2015 | Volume 52 | Issue 3
 Priya, et al.: Pathology of pediatric Ewing sarcoma
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Letter to the Editor
Squamous cell carcinoma arising in an epidermal cyst
Sir,
Epidermal cysts (EC) are commonly encountered in
surgical practice. [1] There are only few reports of such
malignant transformation in the literature.[2,3] We hereby
report a case of squamous cell carcinoma (SCC) arising
in an EC.
A 68‑year‑old man came having complaints about
swelling over the right submandibular region since one
year. The initial small non‑tender and painless swelling
of 2 cm × 2 cm had rapidly increased in size since last
three months. A swelling of about 6 cm × 4 cm was
noted on the right submandibular region. The skin above
the swollen region was normal. An ipsilateral single level
II cervical lymph node measuring 2 cm × 2 cm was
noted. The oral examination was normal. Ultrasound of
the neck revealed a large cystic lesion 5.7 cm × 4 cm in
submandibular angle with thick turbid contents and foci
of calcification with a probable differential diagnosis of
dermoid cyst and epidermoid cyst. A subcutaneous cystic
Indian Journal of Cancer | July-September 2015 | Volume 52 | Issue 3
Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl
J Med 2003;348:694‑701.
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et al. Morphologic and immunophenotypic diversity in Ewing family
tumors: A study of 66 genetically confirmed cases. Am J Surg Pathol
2005;29:1025‑33.
17. Llombart‑Bosch A, Machado I, Navarro S, Bertoni F, Bacchini P,
Alberghini M, et al. Histological heterogeneity of Ewing’s sarcoma/PNET:
An immunohistochemical analysis of 415 genetically confirmed cases
with clinical support. Virchows Arch 2009;455:397‑411.
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remarkable consistency of t(11;22) (q24;q12). Cancer Genet Cytogenet
1988;32:229‑38.
19. Carter RL, al‑Sams SZ, Corbett RP, Clinton S. A comparative study of
immunohistochemical staining for neuron‑specific enolase, protein gene
product 9.5 and S‑100 protein in neuroblastoma, Ewing’s sarcoma and
other round cell tumours in children. Histopathology 1990;16:461‑7.
20. Amann G, Zoubek A, Salzer‑Kuntschik M, Windhager R, Kovar H. Relation
of neurological marker expression and EWS gene fusion types in MIC2/
CD99‑positive tumors of the Ewing family. Hum Pathol 1999;30:1058‑64.
21. Gu M, Antonescu CR, Guiter G, Huvos AG, Ladanyi M, Zakowski MF.
Cytokeratin immunoreactivity in Ewing’s sarcoma: Prevalence in 50 cases
confirmed by molecular diagnostic studies. Am J Surg Pathol 2000;24:410‑6.
22. Collini P, Sampietro G, Bertulli R, Casali PG, Luksch R, Mezzelani A, et al.
Cytokeratin immunoreactivity in 41 cases of ES/PNET confirmed by
molecular diagnostic studies. Am J Surg Pathol 2001;25:273‑4.
23. Elbashier SH, Nazarina AR, Looi LM. Cytokeratin immunoreactivity in
Ewing sarcoma/primitive neuroectodermal tumour. Malays J Pathol
2013;35:139‑45.
24. Oliva E, Amin MB, Jimenez R, Young RH. Clear cell carcinoma of the urinary
bladder: A report and comparison of four tumors of mullerian origin and
nine of probable urothelial origin with discussion of histogenesis and
diagnostic problems. Am J Surg Pathol 2002;26:190‑7.
25. Komatsu S, Watanabe R, Naito M, Mizusawa T, Obara K, Nishiyama T,
et al. Primitive neuroectodermal tumor of the adrenal gland. Int J Urol
2006;13:606‑7.
swelling with cheesy material was noted intra‑operatively.
Complete excision was not possible as the cyst was
adherent to tissue around. Hence, the sac was excised in
bits and sent for histopathological evaluation. Grossly,
there were three irregular tissue bits. The outer surface
was dark brown and the cut surface was gray white,
and one of the bits showed a lymph node measuring
1.5 × 1 × 1 cm. Histopathologically, the multiple
sections from the tissue showed an infundibular type
of EC lined by stratified squamous epithelium, which
was in places hyperplastic [Figure 1] and invasive SCC
composed of neoplastic cells arranged in small sheets,
clusters and masses [Figure 2]. The cells were showing
pleomorphism, nuclear atypia, nuclear hyperchromasia,
individual cell keratinization and increased mitotic figures
infiltrating the underlying skeletal muscle and fibro
adipose tissue. Numerous epithelial pearls were noted
in the center of the neoplastic cell nests [Figure 2].
Inflammatory cells were seen between tumor cells.
A tumor cell‑induced giant cell reaction was noted.
The lymph node showed reactive hyperplasia.
A well‑defined transition between the EC and SCC was
335