Hindawi Publishing Corporation
Case Reports in Oncological Medicine
Volume 2013, Article ID 964568, 3 pages
Bilateral Ewing Sarcoma/Primitive Neuroectodermal Tumor of
the Breast: A Very Rare Entity and Review of the Literature
N. Majid,1M. Amrani,2I. Ghissassi,1M. El Cadi,3M. El Bouzidi,3M. El Kabous,1
A. Kherbach,3and H. Errihani1
1Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco
2Department of Pathology, National Institute of Oncology, Rabat, Morocco
3Department of Gynecology and Obstetrics, Faculty of Medicine and Pharmacy, University Mohammed V Souissi, Rabat, Morocco
Correspondence should be addressed to N. Majid; email@example.com
Received 17 April 2013; Accepted 20 May 2013
Academic Editors: S. Aksoy, J. M. Buchanich, and J. I. Mayordomo
Copyright © 2013 N. Majid et al.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Peripheral primitive neuroectodermal tumors (PNET) are rare malignant tumors, affecting mostly children and adolescents
and have been described in breast in eight case reports only. In this paper, we present a case of bilateral mammary ES/PNET
where distinction between primary and metastatic diseases was discussed through a literature review. The aim of this work is to
demonstrate that although rare, the possibility of PNET should be kept in mind while evaluating a palpable breast abnormality in
a young female.
The ES/PNET family of tumors is part of a rare group
of malignant neoplasms arising from neuroectodermal ele-
ments, with small round cell morphology. This variant typ-
ically occurs in bony structures of adolescents and young
adults . The diagnosis of ES/PNET requires immunohis-
tochemistry analysis and the presence of a t(11;22) transloca-
tion. As a soft tissue neoplasm, PNET arising in the breast
is extremely uncommon; only 8 cases were reported in an
extensive search in the medical literature. To our knowledge,
none had bilateral breast involvement as presented in this
2. Case Report
A 30-year-old woman presented with painless and progres-
sively growing lumps in the right than in the left breast
for 10 months duration. There was no family history of
breast cancer, prior breast mass, trauma, or other associated
symptoms. Examination revealed firm, fixed, painless, and
palpable retromammary bilateral masses measuring 7 and
4cm in the right and left breast, respectively, associated with
skin retraction and bilateral axillary lymph node metastases.
Mammography and ultrasonography identified suspicious
multiple bilateral masses. The lesions were hypoechoic, het-
olar area without evidence of microcalcifications (Figure 1);
axillary lymph nodes were enlarged. The pathology report
of bilateral biopsies performed showed a proliferation of
small, round to oval cells having unconspicuous nucleoli
and scanty cytoplasm with thickened nuclear membrane
and CD99 (Figure 2(b)) but were negative for AE1/AE3,
leukocyte common antigen LCA, chromogranin, and CD56.
Disease progressed rapidly and the patient became symp-
tomatic with considerable dyspnea. A staging workup with
whole body computed tomography scan and bone scintig-
raphy revealed a superior mediastinal mass extending to
the para-aortic area with metastases in the right lung and
a pleural effusion; no bone metastasis was found. Based on
these findings metastatic ES/PNET was the final diagnosis.
Therefore the patient received 2 cycles of VAC IE regimen
doxorubicin 75mg/m2iv bolus d1, vincristine 2mg iv d1
(cyclophosphamide 1200mg/m2iv d1 followed by mesna,
mesna, Etoposide 100mg/m2/d iv d1–5 every 21 days), but
alternating with Ifosfamide 1.8g/m2/d iv d1–5 given with
2Case Reports in Oncological Medicine
Table 1: Summary of primitive neuroectodermal tumors of the breast reported in the literature.
Presentation Size (cm)Disease TreatmentOutcome
Tamura et al.  Breast lump2.1 ×1.8
2.5 × 2
Wide local excision
+ adjuvant chemotherapy
Maxwell et al. 35Breast lump 1.8PrimaryFree of disease at 2.5 years
da Silva et al. 35Breast lump12 ×7.5Primary
Local and pulmonary
relapse; death at 2 years
Free of disease at 6 monthsKo et al. 
Vindal and Kakar
3 × 2
3.5 × 3
PrimaryFree of disease at 36 months
Kwak et al. 49
Mass in the
Metastatic ChemotherapyNot available
Dhingra et al. 26Breast lumpPrimary
Free of disease at 12 months
Suebwong et al. 46 Breast lumpPrimary
Local and pulmonary
The patient’s medical
condition deteriorated, and
she died after 2 cycles of
Majid et al.30
7 and 5 in the
right and left,
Figure 1: The mediolateral oblique (MLO) and craniocaudal (CC)
view of the left and right breast mammogram.
unfortunately she succumbed to respiratory failure due to
pulmonary metastasis and she died.
Ewing’s sarcoma (EWS)/peripheral primitive neuroectoder-
mal tumors (PNET) are small round cell tumors, occurring
primarily in bone and soft tissues of the limbs  and arise
from neuroectodermal elements that probably develop from
migrating embryonic cells of the neural crest .
This group of tumors is characterized by the presence of
the typical translocation (11;22) (q24;q12) and the expression
of CD99 antigen (MIC2) on immunohistochemistry ,
as seen in this case. Children and young adults are most
frequently affected, and our patient was 30 years of age.
As soft tissue neoplasms, PNET/ES have been described
in the kidney, the parotid gland, the chest wall, the ovary,
the rectum, the gall bladder, the retroperitoneal cavity, the
rare location and has been reported only seven times as a
primary tumor and one as a metastatic tumor, in a thorough
search through the medical literature as described in Table 1.
In the present case the distinction between primary and
metastatic PNET to the breast was difficult. On one hand the
clinical history suggested a primary PNET of the right breast
which metastasized to the contralateral breast via lymph
nodes localized along the anterior thoracic wall and then to
breast are from mammary primaries  in which case lym-
phatic metastases are usually found in the medial portion of
the breast, the skin becomes diffusely thicker, and the breast
parenchyma becomes denser on mammography with many
other hand, a primary mediastinal PNET that metastasized
to the lung and the breast is also possible. In approximately
30% of patients, metastasis to the breast is the first sign of
malignancy, and time from initial diagnosis to metastasis
to the breast varies between 1 month to 15 years. Moreover,
some reports emphasize that blood-born metastases to the
breast are bilateral but often well-defined rounded masses
in contrast to the present case . Nevertheless, primary
mediastinal PNET, even if uncommon, are mostly located
in the posterior than in the anterior mediastinum like other
neurogenic tumors .
Management of ES/PNET is usually multimodal, and
patients with metastasis at diagnosis are treated with
Case Reports in Oncological Medicine3 Download full-text
CD99 membranous staining of tumor cells ×40 (b).
the same treatment approach as patients with localized
treatment comprises multidrug chemotherapy (vincristine,
doxorubicin, cyclophosphamide, ifosfamide, and etoposide)
and whole-lung irradiation in patients with lung metastases
[15, 16]. In this case, the patient’s medical condition deterio-
rated, and she died after 2 cycles of chemotherapy.
Prognosis of metastatic disease is generally poor and it does
not seem to make a difference whether the ES/PNET is
primary or metastatic to the breast. The objective of this
case is to emphasize that histopathological confirmation is
mandatory especially in cases of unusual locations.
 N. Friedrichs, R. Vorreuther, C. Poremba et al., “Primitive
neuroectodermal tumor (PNET) in the differential diagnosis of
198, no. 8, pp. 563–569, 2002.
 G. Tamura, S. Sasou, S. Kudoh et al., “Primitive neuroec-
todermal tumor of the breast: immunohistochemistry and
fluorescence in situ hybridization,” Pathology International, vol.
57, no. 8, pp. 509–512, 2007.
 R. W. Maxwell, S. V. Ghate, R. C. Bentley, and M. S. Soo,
“Primary primitive neuroectodermal tumor of the breast,”
Journal of Ultrasound in Medicine, vol. 25, no. 10, pp. 1331–1333,
European Journal of Obstetrics Gynecology and Reproductive
Biology, vol. 137, no. 2, pp. 248–249, 2008.
 K. Ko, A. K. Eun, S. L. Eun, and Y. Kwon, “Primary primitive
neuroectodermal tumor of the breast: a case report,” Korean
Journal of Radiology, vol. 10, no. 4, pp. 407–410, 2009.
pp. e453–e455, 2010.
 J. Kwak, E.-K. Kim, J. K. You, K. K. Oh, S. W. Hong, and S. H.
Kim, “Metastasis of primitive neuroectodermal tumor to the
breast,” Journal of Clinical Ultrasound, vol. 30, no. 6, pp. 374–
 K. K. Dhingra, P. Gupta, V. Saroha, S. Roy, and N. Khurana,
4, pp. 880–882, 2010.
A. Tamnit, “Ewing’s sarcoma and primitive neuroectodermal
tumour (ES/PNET) presenting as a breast mass,” Oncology
Letters, vol. 4, no. 1, pp. 67–70, 2012.
 L. P. Dehner, “Primitive neuroectodermal tumor and Ewing’s
sarcoma,” American Journal of Surgical Pathology, vol. 17, no. 1,
pp. 1–13, 1993.
immunophenotypic diversity in Ewing family tumors: a study
of 66 genetically confirmed cases,” American Journal of Surgical
Pathology, vol. 29, no. 8, pp. 1025–1033, 2005.
 E. S. McCrea, C. Johnston, and P. J. Haney, “Metastases to the
breast,” American Journal of Roentgenology, vol. 141, no. 4, pp.
 S. Y. Chung and K. K. Oh, “Imaging findings of metastatic
disease to the breast,” Yonsei Medical Journal, vol. 42, no. 5, pp.
 S. Pandit, S. Mukherjee, S. Bhattacharya et al., “A rare medi-
astinal tumour in a young male mimicking massive pleural
effusion,” Lung India, vol. 29, no. 1, pp. 66–69, 2012.
 H. E. Grier, M. D. Krailo, N. J. Tarbell et al., “Addition of
sarcoma and primitive neuroectodermal tumor of bone,” The
New England Journal of Medicine, vol. 348, no. 8, pp. 694–701,
 A.Schuck,J.Hofmann,C.R¨ ubeetal.,“RadiotherapyinEwing’s
sarcoma and PNET of the chest wall: results of the trials CESS
81, CESS 86 and EICESS 92,” International Journal of Radiation
Oncology Biology Physics, vol. 42, no. 5, pp. 1001–1006, 1998.