A case report on retroperitoneal PNET/EWS

doi:10.4236/crcm.2013.26098

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Vol.2, No.6, 366-369 (2013) Case Reports in Clinical Medicine

http://dx.doi.org/10.4236/crcm.2013.26098

A case report on retroperitoneal PNET/EWS

Zhanqiang Zhang, Honglan Yu, Yingying Shi, Hanping Shi*

Department of Surgery, The First Affiliated Hospital, Sun Yet-sen University, Guangzhou, China;

*Corresponding Author: [email protected]

Received 12 June 2013; revised 20 July 2013; accepted 1 August 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Primitive neuroectodermal tumor (PNET) and

Ewing’s sarcoma (EWS) are small round cell

tumors occurring mainly in children and ado-

lescents, rarely in adults. It can occur in multiple

tissues and organs including kidney, adrenal,

bladder, liver, small intestine, colon and rectum,

with a preferred location within the chest area, in

the limbs and around the spine, but with rare

cases of abdominal, pelvic or retroperitoneal.

Here we present a case of the retroperitoneal

PENT/EWS in a 38-year-old man and we discuss

the clinical features, histopathological charac-

teristics, diagnosis, treatment and prognosis.

Keywords: Retroperitoneal; Sarcoma; Primitive

Neuroectod er ma l T um or; Ewing’s Sarcoma

1. INTRODUCTION

Primitive neuroectodermal tumor (PNET) and Ewing’s

sarcoma (EWS) are small round cell tumors occurring in

the soft tissues and bones, but rarely in the abdominal

cavity, pelvic and retroperitoneal. Here we present a case

report on the retroperitoneal PENT/EWS in our hospital,

in conjunction with literature review on the topic.

2. CASE PRESENTATION

A male subject of 38 years old, who had left upper

quadrant mass accompanied with pain for 1.5 years and

with enhanced pain since the past 20 days, was admitted

into our hospital on July 2, 2007. The subject received

left kidney + left retroperitoneal tumor partial resection

after revealing a bulky left retroperitoneal tumor by CT

and MR examination for his left upper abdominal pain in

December 2005 at a local hospital. He then began a

chemotherapy program because of the PNET diagnosed

by postoperative pathology in January 13, 2006. The

chemotherapy regimen was ifosfamide 4.0 g on day 1-4

+ epirubicin 100 mg on day 1, 2, and 4. Later, he was

admitted into our hospital after a 8 × 9.6 cm2 cystic

space-occupying lesion in his left kidney had been re-

vealed by CT. The results based on consultation on the

pathological datasheet collected from the hospital where

he received the surgery and chemotherapy indicated that

the tumor cells were small and round with strongly

stained nuclei, thin chromatin, poorly defined nucleoli,

and shrank cytoplasm. The tumor cells were diffused,

partly displaying the daisy-like structure. Immunohisto-

chemistry: CD56 and CD99 (+) large-sheet structure tu-

mor cells, CgA and Syn (+) small number tumor cells,

LCA (−), EMA and CK (−), vimentin and CD34 (−), Ag

tumor cells missing reticular fibers, diagnosed as PENT/

EWS. Laparotomy on May 25, 2006 after appropriate

preoperative preparation displayed the left upper quad-

rant mass up to the diaphragm, down to the left iliac

fossa, medial to the right side of the abdominal aorta,

lateral to the left paracolic gutter. The lump felt hard and

looked smooth and glossy, and was located deep to the

waist big muscle closed to spleen. Thus, a complete re-

section of the whole lump tissue along with the whole

spleen and the diaphragm area adhered and infiltrated by

the tumor. The patient recovered well after the surgery

and was discharged without complications. He continued

the same chemotherapy program at the local hospital. He

experienced recurrence of left upper quadrant pain 20

days ago. MR displayed at left upper quadrant retroperi-

toneal tumor; he was then readmitted to our hospital.

Physical examination: abdomen slightly bulged, left up-

per quadrant palpable mass which was ill-defined with

tenderness and poor mobility, but without other abnor-

malities. Upon completion of all necessary preoperative

routine examination, no obvious abnormalities were found.

The markers for digestive system tumors AFP, CA19-9,

CEA, and CA125 were all at normal levels. CT showed a

round mass either on the left kidney area or retroperito-

neal area, with the upper mass measuring 8 × 8.9 × 8.4

cm3 and the lower one measuring 7 × 7.1 × 5.4 cm3; with

unclear boundary and adhesion to neighboring tissues,

Z. Q. Zhang et al. / Case Reports in Clinical Medicine 2 (2013) 366-369 367

close to the diaphragm; the lower lump wrapped iliac

artery and adhered to gastrointestinal tract. Otherwise,

the patient was in good condition without significant

surgical contraindications. After all preoperative prepara-

tion, we planned to conduct complete resection of the

tumor and its adhesion diaphragmatic with patch repair

and graft replacement for the tumor in the lower position

had iliac artery adhesions. However, in the morning of

the day for operation, the patient had sudden sinus

tachycardia with heart rate of 120 bpm at the time of

indwelling nasogastric tube. The surgery had to be inter-

rupted. The patients were under monitoring for several

days. His heart rate decreased, but remained relatively

high compared to baseline heart rate. The patient and his

family members asked for provisional discharge. After-

wards, his tumor grew rapidly, but because of the diffi-

cult financial situation, he has not received surgery any

more. He died of gastrointestinal obstruction, malnutri-

tion, and cachexia 37 days after being discharged.

3. DISCUSSION

3.1. Overview

PNET and EWS are malignant tumors composed of

small round cells, frequently occur in the soft tissue and

bone but are very rare clinical cases. They have a com-

mon neuroectodermal origin, with similar morphological

conformation, specific chromosomeal translocation which

is related to the EWS gene on chromosome 22, belong-

ing to the PNET/EWS family tumors [1]. PNET and

EWS were once believed to be different types of tumors

because of their different differentiations: PNET belongs

to neuroectodermal differentiation whereas EWS tends to

be undifferentiated. With the advances of immunohisto-

chemistry, electron microscopy, and genetic pathology,

bone Ewing’s sarcoma, bone Ewing’s sarcoma, the pe-

ripheral neuroepithelioma or primitive neuroectodermal

tumor, Askin’s tumor, as well as other types of tumors

with their classification still in debate are now all con-

sidered as PNET/EWS family tumors [2-4]. A growing

number of studies suggest that between PNET and EWS

there are no significant differences in terms of their

treatment and prognosis. The first case of PNET/EWS

family tumors was reported in 1918 by Stout. In recent

years, with the development of immunohistochemistry

and electron microscopy techniques, our understanding

of PNET/EWS family tumors have been gradually deep-

ening and reports on this condition have been steadily

increasing. PNET/EWS occurs mainly in children and

adolescents, rarely in adults. It can occur in multiple tis-

sues and organs including kidney, adrenal, bladder, liver,

small intestine, colon and rectum, with a preferred loca-

tion within the chest area, in the limbs and around the

spine, but with rare cases in abdominal, pelvic or retrop-

eritoneal.

3.2. Clinical Manifestations

Clinical manifestations depend on the site and the size

of the tumor, and the invasion of the surrounding organs.

The rapid growth accompanied by pain, lumps, and

compression symptoms caused by the tumor is the most

common manifestation [5]. Other manifestations include

fatigue, weight loss, fever, and various gastrointestinal

symptoms such as abdominal distension, nausea, and

vomiting.

3.3. Auxiliary Examination

There have not been any clinical laboratory tests and

specific biomarkers for this type of tumor. B ultrasound,

CT, and MR are mainly used to depict tumor internal

structure, the scope of violations as well as relations with

the surrounding tissue, and meanwhile to provide the

information as tumor metastasis, which is of paramount

clinical importance for preoperative evaluation of the

resection scope and the anticipated efficacy. Imaging

often shows soft tissue mass, invasive growth, tendency

to invade surrounding tissue, and unclear boundaries

with the surrounding tissue structure. In addition to the

small size, the tumor generally has uneven density. Un-

der CT, the tumor mostly shows uneven density with

visible internal cystic and necrosis, which are worsened

by tumor enlargement [6]. If a tumor is seen in the pre-

ferred sites with obvious invasion, easy liquefaction and

necrosis, as well as incomplete capsule and the separator

inside the tumor, especially if when obvious tumor

thrombus can be seen in the surrounding intravascular,

then the possibility of PNET should be considered [7].

The definite diagnosis still relies on biopsy and patho-

logical examination. To prevent the spread of the tumor

and the needle tract transfer, preoperative percutaneous

biopsy is generally not recommended, unless the tumor is

unresectable and needs radiotherapy and chemotherapy

[8].

3.4. Pathology

Tumor specimens: oval, lobulated or irregular in shap;

infiltrative growth; incomplete capsule, size ranging

from 3 cm × 2cm × 1 cm to 40 cm × 20 cm × 5 cm; sec-

tions are gray or sallow in color, solid and brittle or soft,

fish-like hemorrhagic necrosis in texture [9]. Morpho-

logical characteristics include malignant tumor mass

with small round cells, visible small focal necrosis and

spread necrosis under a light microscope, which may or

may not form the Homer-Wright rosettes. CD99 (MIC2)

is uniformly and diffusely expressed on the cell mem-

brane of the tumor, and vimentin, NSE, Syn, of Cag, NF,

and S-100 are also expressed to varying abundances.

Z. Q. Zhang et al. / Case Reports in Clinical Medicine 2 (2013) 366-369

368

Glycogen granules or nerve secretory granules can be

seen under an electron microscope [9,10].

From the molecular pathological view, PNET/EWS

have the same t(11; 22) (q24; q12), or less t(21; 22) (q22;

q12) or t(7; 22) (p22; q12). All these chromosomal rear-

rangements fuse the EWS gene on chromosome 22 to

FLI21 ERG or ETV1 gene members of the ETS tran-

scription factor family, resulting in EWS/FLI21, EWS/

ERG or EWS/ETV1 fusion genes, leading to tumori-

genesis. 95% of the tumors can be detected by RT-PCR

and FISH with high sensitivity and specificity [11].

Identification and diagnosis of this type of tumor pri-

marily relies on comparisons with other intra-abdominal

and retroperitoneal soft tissue tumors, including the loca-

tion, age, tumor morphological alterations, immunohis-

tochemical illustration, and genetic traits.

3.5. Treatment and Prognosis

PNET/EWS is a systemic disease and its therapy re-

quires comprehensive treatment, including surgery, ra-

diotherapy, chemotherapy and biological therapy. There

is no uniform regimen for intraperitoneal or retroperito-

neal PNET/EWS. Rud et al. [12] and Covelli et al. [13]

suggested that the surgery may be more important for

EWS outside bone than EWS in the bone and total resec-

tion yields better prognosis. Based on the literature,

complete surgical removal may be the most effective

means for cure; even for patients with local recurrence, if

possible, surgical treatment should be implemented. In

order to ensure complete resection, removal of some ad-

jacent organs, the most commonly kidney, adrenal, colon,

pancreas, and spleen, is often necessary. With the devel-

opment of vascular surgery, resection of involved vessels

and implantation of artificial blood vessels may be coap-

plied, though the long-term efficacy and benefits await

further studies to confirm.

As far as radiotherapy and chemotherapy, there are

different views. Kinsella et al. [14] believed that high

doses of local radiotherapy and VAC procedures are

adequate for EWS outside bone and total surgical resec-

tion may be unnecessary. Local adjuvant radiotherapy

after complete resection cannot significantly reduce the

local recurrence because of high doses and side effects

that require stringent protective measures [12,15]. Ven-

kitaraman et al. [16] proposed that intensive chemother-

apy is necessary after complete resection of the tumor or

radiotherapy with doses >50 Gy, for patients with PNET/

EWS sarcoma outside bone in order to obtain good effect.

Of 14 PNET/EWS patients without metastases who un-

derwent combinational chemotherapy (5 with VAC pro-

cedures, 5 with VACA procedures, four with VAC/IE

procedures), 8 were cured, 2 partially cured, and 4 had

progressive deterioration [16].

Venkitaraman et al. [16] believed that high hemoglo-

bin, low lactate dehydrogenase, VAC/IE chemotherapy,

and complete response to chemotherapy are the factors

for raising tumor-free survival rate and overall survival

rate. Martin et al. [15] considered the initial perform-

ance of tumor (primary or recurrent) is an important pro-

gnostic factor, whereas tumor location, size, and age

make no statistical significance [15,16]. PNET/EWS pa-

tients without metastatic who received combination ther-

apy had 5-year survival rate of 60% and overall survival

rate of 30% [16]. Aggressive PNET/EWS causes distant

metastases at early stages, frequent local recurrence and

regional lymph nodes, lungs, liver, bone and bone mar-

row metastasis, and has poor prognosis with the median

survival time of about two years; the leading cause of

death is metastasis to the lung, bone, liver and other or-

gans.

4. CONCLUSION

The abdominal cavity and retroperitoneal PNET/EWS

are relatively rare, but they grow rapidly in larger size,

oppress surrounding organs and large vessels, and make

surgical resection difficult. It is often in high degree of

malignancy and already has widespread subclinical me-

tastasis at the time of going to a clinic. Moreover, it can

quickly transfer to everywhere throughout the body ren-

dering poor prognosis. Clinicians should be highly alert

to this condition. Imaging is the primary means of early

detection and early diagnosis. Complete surgical resec-

tion may be the most effective way of cure. Whenever

possible, surgery should be implemented even in patients

with local recurrence. In order to ensure complete re-

section, removal of any neighboring organs, most com-

monly kidney, adrenal, colon, pancreas, spleen, and so on,

may be required. With the development of vascular sur-

gery, resection of involved vessels and implantation of

artificial blood vessels may be conducted. The efficacy

of radiotherapy is still unclear. Future studies are war-

ranted to develop surely effective surgical treatment op-

tions and preoperative/postoperative adjuvant therapies.

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